The Azzurri take on the European champions in Lisbon, with Nice striker Balotelli set to miss his first game since being brought back into the fold by Mancini when he took over last May.
Lorenzo Pellegrini has also been left out along with Cagliari goalkeeper Alessio Cragno, Juventus defender Daniele Rugani and Roma midfielder Nicolo Zaniolo.
Mancini confirmed Fiorentina forward Federico Chiesa would start after the 20-year-old proved pivotal when he came on last Friday, along with goalkeeper Gianluigi Donnarumma.
Balotelli came under fire for his performance in their Nations League opener against Poland on Friday, where they were held 1-1.
The 28-year-old was substituted with a muscular problem, with Mancini conceding his fitness level was a problem.
But the former Manchester City boss defended his player from criticism.
“A player knows when he has played well or badly,” he said.
“I think Mario knows full well what his performance against Poland was like. Criticism is part of the game.
“We are only at the beginning of this journey and will change several players from the Poland game, also to look after the lads.
“We are ready and know it can be a very important match. I won’t say it’s decisive, as there are another two to go, but we are facing the reigning European champions.”
Italy have won six games to four against Portugal in previous meetings, but the Azzurri have not won a game in Lisbon in 31 years.
Mancini took charge of the national team after the four-time World Cup winners’ failure to qualify for Russia.
Balotelli has played in all four games so far under Mancini, scoring in a 2-1 friendly win over Saudi Arabia. Mancini’s other two friendlies were a 3-1 defeat to World Cup winners France and 1-1 draw with the Netherlands.
Balotelli has made the trip to Portugal with the squad as Mancini considers him to be a central figure in the team he is trying to rebuild.
Balotelli’s place could be taken by either Andrea Belotti or Ciro Immobile.
Olivier Giroud‘s thumping volley earned world champions France a 2-1 Nations League win over the Netherlands in Paris.
The Chelsea striker, who failed to score during the World Cup in Russia, met Benjamin Mendy’s left-wing cross with a fierce first-time finish in the 75th-minute.
Jasper Cillessen in the Holland goal got a hand to the shot, but could not keep it out as Didier Deschamps’ men won for the first time in Group A1.
Kylian Mbappe, one of the stars of the World Cup triumph, had set France on their way after 14 minutes, tapping home at the far post from a Blaise Matuidi cross after Quincy Promes’ horribly misplaced header had sent the Juventus man clear.
But Holland stunned the home fans in the 67th minute when, moments after Georginio Wijnaldum dragged a glorious chance wide, Ryan Babel poked home a pin-point low cross.
Wales were brought back down to earth following their 4-1 thrashing of the Republic of Ireland as Denmark, back at full strength, cruised to a 2-0 win in Aarhus.
Christian Eriksen, one of the senior players to return to the squad following the resolution of the players’ image rights row, which had led to a team of lower-league and futsal players taking to the field in the 3-0 friendly defeat to Slovakia on Wednesday, was on target twice in the Group B4 clash.
He produced a smart low finish off the side of a post in the 32nd minute and sealed the victory with a 63rd-minute penalty after Ethan Ampadu was harshly adjudged to have handled Viktor Fischer’s cross.
Ukraine earned a 1-0 win at home to Slovakia in Group B1 thanks to an 80th-minute penalty from West Ham’s Andriy Yarmolenko.
In Group D1, Georgia also struck late as a 77th-minute penalty from Tornike Okriashvili finally broke Latvia’s resistance to earn a 1-0 win for the hosts.
Bulgaria were also 1-0 winners at home, Radoslav Vasilev’s second-half goal seeing off 10-man Norway, who lost Haavard Nordtveit to a second yellow card in the 88th minute of the Group C3 match.
In the same group, Petar Stojanovic’s own goal in the 89th minute earned Cyprus a 2-1 home win over Slovenia.
Robert Beric had put the visitors in front before Pieros Sotiriou levelled.
Ezgjan Alioski with a penalty and Goran Pandev were on target in a 2-0 Group D4 win for Macedonia over Armenia.
In the same group, Liechtenstein won 2-0 at home to Gibraltar thanks to goals from Dennis Salanovic and Sandro Wieser.
Al Jazira Sports and Culture Club (JSCC) has a new CEO.
Nick Garcia has been appointed as Group Chief Executive Officer, overseeing all club activities.
Nick has over 20 years of global and local experience in sport. He spent five years working in Abu Dhabi from 2008-2012, building one of the region’s leading sports marketing agencies, CSM Middle East. In 2012, Nick relocated home to the UK, where he took a leadership position at Manchester City FC, helping to devise and execute the group commercial strategy through it’s transformation to City Football Group.
Dr. Sultan Ahmed Al Jaber, Vice Chairman of the AJSC Board and Chairman of the Executive Committee said: “On behalf of the Al Jazira Sports and Culture Club Board I would like to thank His Highness Sheikh Hamdan bin Zayed Al Nahyan, the Ruler’s Representative in Al Dhafra Region, Honorary Chairman and Chairman of the JSCC Honorary Board as well as His Highness Sheikh Mansour bin Zayed Al Nahyan, Deputy Prime Minister and Minister of Presidential Affairs, Vice Chairman of the JSCC Honorary Board and Chairman of the JSCC Board of Directors for their continued guidance and support for the Club. I would also like to thank the members of the JSCC Board of Directors and the executive management team for their hard work in developing the club over recent months. I welcome Nick to the Club and wish him the best of luck in his new mandate.”
He added: “Our ability to achieve the strategic goals for the Al Jazira Club will depend largely on supporting our teams in their aspirations to achieve additional successes and championships. We will continue to instill the spirit of operational excellence, positivity, diligence, perseverance and teamwork to ensure that the Al Jazira Club continues to be the pride of Abu Dhabi.”
On his part Nick explained: “I am delighted to take up the position of Group Chief Executive Officer of JSCC in my second home, Abu Dhabi. The great ambitions of the JSCC board for the future of the club and its commitment to realizing these aspirations have been instrumental in my decision to join team Al Jazira, which has the potential to become a best in class organisation both on and off the field of play. ”
Nick highlighted that the next phase of the club will focus on improving operational efficiencies, ensuring a sustainable financial position, smart investments, increasing the Club’s revenues across its businesses as well as enhancing the spirit of competitiveness and strengthening the club’s overall brand. He emphasised that achieving these goals will require hard work, patience, proper planning, perseverance and the diligence of all team members.