The 31-year-old has missed the last two Premier League games with ankle problems and has not travelled with the team for the first leg in Brussels.
"He's not happy with his condition," said manager Jose Mourinho. "He has a bad feeling with his ankle."
Asked if Rooney will be fit for the visit of Chelsea in the Premier League on Sunday, Mourinho added: "Let's see".
Goalkeeper David de Gea is in the squad despite missing the 3-0 Premier League win over Sunderland last Sunday, although it is expected that Sergio Romero will keep his place in the team.