The Portuguese winger was substituted towards the end of the 0-0 draw at Villa Park after picking up the knock.
Dimitar Berbatov is already out of Tuesday's game in Spain, and United boss Sir Alex Ferguson confirmed Ronaldo could join the Bulgarian on the sidelines.
Ferguson said: "His leg is in a mess. He is doubtful for Tuesday."
The United manager also felt referee Chris Foy made the correct decision in not awarding a penalty following some shirt pulling by Nemanja Vidic on Villa striker Gabriel Agbonlahor.
He added: "Vidic has got the ball. The crowd can sometimes get you a penalty, but the referee couldn't give that one. He gave plenty to them as it was."
Wayne Rooney wasted United's best chance of a game with few clear-cut opportunities and Ferguson was satisfied with his team's display.
"I thought we were the better team apart from a 15-minute spell at half-time when Villa got the ball into our box from free-kicks and corners and caused a lot of problems," said Ferguson.
"Apart from that, we weren't in danger. I was pleased with the effort we put in against an aggressive and determined team who defended for their lives.
"Our possession was good and we created the chances. Wayne Rooney and Ji-Sung Park had good chances.
"With the amount of possession we had at the end I thought another chance must come along, but they held on."