Italy could name 10 of the 11 starters who began the win against Belgium in their opening game.
Antonio Candreva is out with a thigh problem and his place at right wing-back is expected to go to Roma's Alessandro Florenzi.
Spain have named the same starting line-up in all three games so far.
Centre-back Sergio Ramos is the only Spaniard to have been booked and another caution would rule him out of a potential quarter-final.
Monday's meeting of Mediterranean superpowers brings together familiar foes - it will be the sixth time Italy have met Spain at the finals of the European Championship, making it the most played fixture in the tournament. That history is primarily recent - this will be their fourth Euros encounter since 2008.
Prior to that point, the Spanish regarded the Azzurri as their bogey side - opposition not technically superior but feared because of their perceived mastery of football's dark arts; streetwise, defensive, occasionally cynical and invariably successful.
But now the boot is on the other foot. Spain's shoot-out win against the Italians at Euro 2008 - the first time they had beaten them at a major tournament - proved a definite turning point.
This will be the fourth time the sides have met in the last three European Championships, and the sixth overall - making it the most played fixture in the tournament.
Italy's last competitive win against Spain was a 2-1 victory in the quarter-finals of the 1994 World Cup. Azzurri coach Antonio Conte started that match.
Since then, Spain have lost just one of 11 games against Italy (including friendlies), winning four matches and drawing six (two penalty shoot-outs counted as draws).
Defeat to the Republic of Ireland was the Azzurri's first defeat in 13 competitive games under Antonio Conte (W9, D3).
Italy have failed to score in three of their last four knock-out games at the European Championship - with the exception their 2-1 win against Germany in the semi-finals in 2012.
The Azzurri used more players (22) than any other side in the group stage, including all 20 outfield squad members. Only Leonardo Bonucci and Andrea Barzagli have started all three games.
Italy have never scored more than two goals in their 36 games at the European Championship.
Defeat would see the Azzurri lose consecutive games at the European Championship finals for the first time.
The Spanish have lost three of their last six games at the World Cup and European Championship - as many defeats as in their previous 31 major tournament games.
None of Sergio Ramos' 48 shots at World Cup or European Championships have resulted in goals (excluding penalty shoot-outs).
Alvaro Morata's tally of three European Championship goals for Spain is exceeded only by David Villa (four) and Fernando Torres (five).