Guglielmo Vicario, Moise Kean, Andrea Colpani, Cristiano Biraghi and suspended Giovanni Di Lorenzo are in the stands when Italy host North Macedonia.
It kicks off at the Stadio Olimpico in Rome at 19.45 GMT.
Coach Luciano Spalletti named the expected starting XI in a 4-3-3 formation, but the surprises were on the bench.
It had been known that Tottenham Hotspur goalkeeper Vicario was struggling with flu symptoms, which is why Atalanta shot-stopper Marco Carnesecchi was called up only yesterday and takes a spot on the bench.
Juventus striker Kean had at first seemed to be one of the candidates to play in the starting trident, but instead is not even on the bench, so clearly his fitness levels in training must’ve caused concerns.
Napoli captain Di Lorenzo is suspended, while Fiorentina captain Biraghi and Monza newcomer Colpani are also left out.
Numerous players had already withdrawn or not been called up due to injury, including Giorgio Scalvini, Mateo Retegui, Lorenzo Pellegrini, Manuel Locatelli, Ciro Immobile, Rafael Toloi and Alex Meret.
Why is it a surprise kean is not playing should never be called up in the first place.
A good side but the strikers should be accurate towards the goal.Italy is the best in Europe.Forza Italia
Not enough simple Messi like crosses in the six yard box, too many going for glory and missing otherwise Italy would get a lot more goals in.