The Netherlands striker was withdrawn at half-time during his country's victory against Turkey on Tuesday and must be a doubt for the Old Trafford encounter with the high-flying Saints.
Antonio Valencia and Javier Hernandez also need to be monitored after their international exertions and all three look set to face late checks before the return to Barclays Premier League action.
"We've got a few who came back with a few bumps and bruises," the manager told MUTV. "Probably the one we're most worried about is Robin van Persie. Antonio is very late coming back from South America. Chicharito too. They're the ones who always have long-haul flights. But we're a bit worried about Robin and the condition he's come back in. We'll see how he is tomorrow.
"He got a kick in the calf and he came off at half-time in the second game. He had a kick in the calf and he also had problems with his toes as well. We'll see how he is."
Moyes was also quick to pay tribute to van Persie for overtaking Patrick Kluivert's all-time goals tally for the Netherlands.
"It's an incredible achievement and I've spoken to him about it," added the boss. "I think what he wants to do now is go on and score more goals for Holland and do it in the World Cup where it matters. There have been some brilliant Dutch centre-forwards over the years - to be at the top of that list is something special for him."