The 30-year-old scored a hat trick in the 3-0 win – which completed a 3-2 aggregate victory – but was forced off in the final moments of the match, much to the concern of the home bench.
David Moyes' men did everything perfectly on the night, as they overhauled the 2-0 deficit from the first leg to progress to the quarterfinals. But the Scot now faces being without his match-winner for a prolonged period of time.]
However, Moyes told Sky Sports after the game: "It doesn't look that bad. I've just gone in to see him just now. He's certainly had a knock in and around the knee area, so we don't know exactly. Could be just [that he took] a knee in the back of his knee.
"Not many people score a hat trick in Champions League football," he added of the Dutchman's performance, "And it was a great hat trick as well."
Danny Welbeck, Wayne Rooney and Javier Hernandez will all be able to step into the breach should it be required but Van Persie's absence will hit the under-fire boss hard.
He looked back to his best during the tie, with his movement and touch causing the Greek champions problems throughout, but may see his return to form cut short in the most bitter of ways.