Giorgio Chiellini was on Wednesday ruled out of Italy's World Cup qualifying deciders with Switzerland and Northern Ireland after failing to recover from a thigh injury.
The European champions' captain was among those in doubt for the key matches in qualification for the 2022 tournament in Qatar but the Italian Football Federation said he will leave the national team's training camp on Wednesday.
Chiellini's absence is a big blow heading into Friday's clash in Rome against the Swiss, who trail Group C leaders Italy on goal difference with two games remaining for both teams.
The pair are the only sides in contention for the group's sole guaranteed place at the World Cup, which will be played over November and December next year.
Italy face Northern Ireland at Windsor Park in their final match on Monday, while Switzerland host Bulgaria.
Azzurri coach Roberto Mancini has lost both Euro 2020 icon Chiellini and starting centre-forward Ciro Immobile in less than 24 hours, and is also sweating on the availability of Inter Milan midfielder dynamo Nicolo Barella.
Injured Roma midfield pair Lorenzo Pellegrini and Nicolo Zaniolo were on Monday replaced by Immobile's uncapped Lazio teammate Danilo Cataldi and Atalanta's Matteo Pessina, who has only just returned from over a month on the sidelines.
Pessina, 24, was brought on as a stoppage-time substitute in Atalanta's 2-1 win at Cagliari on Saturday, his first appearance since a calf injury picked up in a home defeat at the hands of AC Milan in early October. (AFP)

Brume, Okezie join global stars for Kip Keino Classic
NPFL confirms May 24 season end date
NCF proposes elite cricket league
Trump envoy wants Italy to replace Iran at World Cup — Report
Gala intensify Osimhen’s special recovery plan
Core Afrique stages first NBF-sanctioned pro event
Professional, amateur golfers tee off at landmark Edo event
Ndidi resumes training after injury layoff
NPFL halts season for Federation Cup
National school volleyball championships begin in Lagos
AFN opens World Relays camp in Lagos
NOC Mourns Galadima, Describes Late Administrator As ‘Principled Visionary’
Rangers International going, going . . . (63,720 views)
Amaju Pinnick: A cat with nine lives (55,047 views)
Second Term: Amaju Pinnick, Other NFF Heavyweights Home to Roost •How Pinnick Broke the Jinx (52,970 views)
Current issues in Nigerian sports: Matters arising (52,564 views)
Sports Development: Zenith Bank on the zenith (52,496 views)
Missing $150,000 IAAF Grant: Solomon Dalung’s Hide and Seek game (52,396 views)
Gov. Abdullahi Ganduje’s solid footprints, commitment to sports development in Kano State (52,249 views)
NFF Presidency: Pinnick, Maigari, Ogunjobi, Okoye in Battle for Supremacy (51,792 views)
Olopade, BET9A wave of revolution in NNL (50,984 views)
Commonwealth Games 2018: Shame of Muhammadu Buhari, Solomon Dalung (49,491 views)
Ibrahimovic’s Man U exit: Whose decision is it? And in whose interest? (47,903 views)
John Mikel Obi: Segun Odegbami’s Outrageous Call! (47,369 views)