The 17-year-old suffered a minor injury during Spain's 1-0 win over Denmark on Saturday evening, and he is not expected to be risked for the team's contest against Serbia.
Alex Baena could therefore come in for a start, with the 23-year-old set to be benefit from La Roja's injury situation, with a number of key players currently unavailable for selection.
Unai Simon, Dani Carvajal, Robin Le Normand, Rodri, Dani Olmo, Gavi and Nico Williams are among those currently on the sidelines, and Yamal is likely to join that list ahead of this match.
Martin Zubimendi scored the winner against Denmark, and the Real Sociedad midfielder is set to feature in the starting side, while Fabian Ruiz should continue in the middle.
Head coach Luis de la Fuente is likely to make a change at left-back, though, with Marc Cucurella expected to be introduced for Alex Grimaldo on Tuesday night.
Pedri and Mikel Oyarzabal should keep hold of their starting spots in the final third of the field, while the Spain line should again be led by Alvaro Morata, who has 36 goals in 81 appearances for his country.
Sergio Gomez, Oscar Mingueza and Bryan Zaragoza, meanwhile, will be hoping to earn just their second caps for Spain.
Spain possible starting lineup: Raya; Porro, Vivian, Laporte, Cucurella; Zubimendi, Ruiz; Baena, Pedri, Oyarzabal; Morata