Ireland face Scotland in the second round of the Six Nations in Murrayfield on Saturday, with the Men in Green looking to bounce back after suffering a commanding defeat to England last Saturday.
Elsewhere, Wales will be bidding to make it 11-successive wins when they take on Italy in Rome.
In the final match of the weekend, an England side purring with confidence will entertain France at Twickenham, aiming to continue their strong start to 2019.
Here, we take a look at the key highlights ahead of each game.
SCOTLAND V IRELAND (Saturday, 18:15)
Talking point – Ireland reaction needed
Losing CJ Stander, Dev Toner and Garry Ringrose to a squad already down serious numbers at 4, 5 and 9 will be a test at Edinburgh, especially after suffering a comprehensive 32-20 defeat to England in round one.
Ireland face an ever-improving Scotland side in the group stages at the World Cup in September, so the dress rehearsal and how they react to last week’s loss will be worth watching alone.
Key battle – Finn Russell v Johnny Sexton
Sexton may not have enjoyed his finest night in a green jersey last week, with his kicking and distribution generally poor.
But the 33-year-old will be crucial to the No10 battle this weekend with his game management, pace, passing and place kicking all key to putting Joe Schmidt’s side on the front foot.
In Russell, Scotland boast an equally influential player, who looks like a new man since his move to Racing 92 in Paris during the summer.
If the 26-year-old can keep his tactical kicking accurate and stretch Ireland to the limit with his flat, searching passes then the Scots could gain a foothold in the contest.
A humdinger of a duel.
What we think – Ireland to win by 12
Gregor Townsend’s side did show some sharp decision making in their victory over Italy, but the complacency to concede three late tries has raised a weakness in their armoury. Ireland will be desperate to avenge their defeat to England, and with key men growing into form, should win this contest easily enough in the end.
ITALY V WALES (Saturday, 20:45)
Talking point – Wales set to equal record
It may have been a slow and inconsistent performance in the win over France, but Wales should have no problem equalling their all-time unbeaten record of 11 games against Italy in Rome.
Whole-sale changes are expected to be made by Warren Gatland in a bid to rest some star names for their round-three clash against England in two weeks time.
But momentum is everything and there is an argument he should keep his star names together in preparation for Eddie Jones’ side.
A bonus-point win in the Italian capital will keep confidence high, but the main focus will be on February 23.
Key battle – Tommaso Castello v Jonathan Davies
Hadleigh Parkes may be the chief lieutenant in the Wales midfield, but Davies is equally as effective with ball in hand and in defence.
The 30-year-old is set to captain the side for the first time, and will provide a fresh cutting edge to Wales’ attack. His slick feet also allows him to evade would-be tacklers and gain extra yardage in a bid to unlock the speed out wide.
In Castello, Italy possess a similar figure, with solid footwork, speed and power, but devoid of the same play-making style of Davies.
Whoever can gain a foothold in this battle will have the upperhand in unlocking the opposition defence and initiating attacking opportunities.
What we think – Wales to win by 25
Italy may be improving, but they will be no match for the pace and power of Wales. Even with large changes expected, Gatland’s side will have too much accuracy in attack and strength in defence for the Azzurri.
ENGLAND V FRANCE (Sunday, 19:00)
Talking point – England back to their best
For all the chat about England’s so-called demise under Eddie Jones, they look a rejuvenated side again after a positive Autumn campaign and commanding win over Ireland, executing some attractive attacking play and serious physicality in defence.
France beat themselves in the game against Wales, imploding when leading with ten minutes to go. With the Red Rose starting to sparkle again, a routine win is expected versus an inconsistent Les Bleus side.
Key battle – Billy Vunipola v Louis Picamoles
The Saracens man looks to be getting closer to the peak of his powers and looks primed to contain the dominance of Picamoles in London.
The 26-year-old has been instrumental this season – when fit – with his strong carrying and tackling all serious threats.
A high-class operator at the breakdown, Vunipola will need to cut down the impact of Picamoles – with the Montpellier man among France’s best performers against Wales in round one.
He made 10 tackles and 14 carries in a virtuous display at Stade de France, and will be key to Les Bleus’ fortunes at the breakdown against an imposing England back-row.
Both players are class acts, but Vunipola has shown before that he is up for any challenge no matter how big the task is.
What we think – England to win by 13
Jonny May, Jack Nowell, Henry Slade and Owen Farrell can all make the magic happen with ball in hand, and will be difficult to stop when going forward at pace.
With the Vunipola brothers shining, the Red Rose will benefit from their powerful ball-carrying.
Expect it to be a tight first half and then the hosts to storm to a convincing win.
Ireland will be without influential centre Garry Ringrose and stalwart lock Devin Toner when they face Scotland in the Guinness Six Nations on Saturday.
Leinster midfielder Ringrose has a hamstring injury, while Toner aggravated an existing ankle problem in Saturday’s 32-20 defeat by England in Dublin.
Wing Keith Earls appears to have proved his fitness after a hip concern by training on Tuesday, but Ireland must now travel to Edinburgh without three key operators, with CJ Stander already missing due to facial fractures.
Ireland confirmed their mounting injury issues on Tuesday, with head coach Joe Schmidt now facing a significant reshuffle of his resources.
Scrum coach Greg Feek said: “Devin’s ruled out for this week with his ankle and Garry Ringrose also. His hamstring isn’t quite right so he won’t be with us either.”
The absence of Leinster lineout specialist Toner will prove the biggest miss to boss Schmidt and Ireland.
The 32-year-old has only missed six Test matches since Schmidt took the helm in November 2013, with the Kiwi coach drawing heavily on his set-piece acumen.
Ireland approached this year’s Six Nations appearing in a position of strength at lock, but were struck by injuries to Iain Henderson and Tadhg Beirne before the tournament started.
Ulsterman Henderson’s finger problem and Munster star Beirne’s knee complaint thinned Ireland’s locking stocks and Toner’s absence will heavily test Schmidt’s squad depth.
Connacht’s Quinn Roux looks set to slot into Ireland’s second row alongside James Ryan, with Ultan Dillane poised to take a seat on the bench.
Munster lock Billy Holland has also been added to Ireland’s squad this week as further cover.
“Quinn did really well at the weekend, he came on and put in a couple of big hits,” said Feek.
“He’s been leading the lineout at Connacht this year, and he’s really progressed there and matured as a player.
“Luckily for us, we have good depth there at the moment.”
Ringrose’s absence could tempt Schmidt into shifting Robbie Henshaw back into the centres, after the Leinster star struggled with his move to full-back in last weekend’s England loss.
Munster’s Chris Farrell and Ulster’s Will Addison are further midfield options for Schmidt, while Rob Kearney could return at full-back.
England hope that Maro Itoje will return in time to reinforce the final stage of their Six Nations title pursuit after being struck down by a knee injury.
Itoje will miss the clashes with France and Wales due to a grade two medial ligament tear sustained in the second half of Saturday’s remarkable victory over Ireland at the Aviva Stadium.
But if his rehabilitation progresses well, the British & Irish Lions lock could be back for the last two rounds against Italy and Scotland.
Offsetting the news of his absence is the return to fitness of flanker Brad Shields, centre Ben Te’o and wing Joe Cokanasiga, who missed the stunning start to the championship in Dublin through injury.
“Maro had the scan and saw a specialist yesterday (Monday). It’s ligament damage to his knee,” forwards coach Steve Borthwick said.
“We anticipate him being able to play at the latter part of the tournament. Hopefully he’ll heal fast and we’ll have him back ASAP.
“Which game that is for depends on how his rehab goes over the next couple of weeks, but we’d expect him to feature later on.”
As cover, Itoje’s Saracens team-mate Nick Isiekwe has been called into England’s 35-man training squad that has assembled to begin preparations for Sunday’s visit of France to Twickenham.
Courtney Lawes, who was a second-half replacement against Ireland, and Joe Launchbury are competing to fill the vacancy in the second row alongside George Kruis.
Itoje will remain at the squad’s Surrey training base to continue his rehabilitation and in the meantime England must decide how to cover for the loss of a player who Eddie Jones believes will soon be recognised as the best lock in the world.
“Maro’s a fantastic player and a great personality around the squad. Clearly it’s significant that he’s out, but we have a lot of brilliant players in his position,” Borthwick said.
“You’ll always miss a player of his calibre, you’ll take some strength out of your team, but we have very good and experienced players to come in.
“It was a tough decision to leave Joe out against Ireland and he was brilliant in the way he supported the team, which is great credit to him.
“We all saw the impact Lawes had off the bench, the hitting power he has and how he can carry.
“We approach team selection by picking the team that we want to get the result for that weekend. We always look at different combinations and we’ll be doing that over the next few days.”
Itoje sustained the injury to his right knee in the second half of England’s remarkable win at the Aviva Stadium when being cleared out of a ruck by Ireland flanker Peter O’Mahony.
He was ruled out for five weeks after suffering a chipped patella to the same knee in the build-up to the autumn series, playing throughout November until the nature of the injury was discovered.