Cristiano Ronaldo, Ryan Giggs and Owen Hargreaves were left out of the squad which faced Arsenal on Saturday, and Paul Scholes was restricted to a 20-minute runout as Sir Alex Ferguson's side won 4-0.
The quartet should all be in contention to start, however, as United resume their European campaign against the French champions.
"I gave them a rest, although Ronaldo had a bit of a tummy upset," Ferguson told Manchester United's official website.
"I was thinking about resting him anyway and perhaps put him on the bench, but when we found out he wasn't well, we decided to give him a complete break.
"The likes of Ryan and Paul Scholes - players with great experience - will play in Lyon on Wednesday. They'll be very important for us."