The Dutchman spent three years at United, winning the Premier League title in his first season at the North-West outfit, before moving to Turkey in 2015.
Van Persie's switch to United was a controversial one as he ended an eight-year spell at Arsenal to join their rivals in a £24m deal.
Ahead of tomorrow's Group A match, the 33-year-old told MUTV: "It will be a special occasion and a special game for me.
"I know Manchester United want to be in the Champions League, but it is how it is now and for me it is a very special group in the Europa League. In the last match I had a game against one of my first teams, Feyenoord, and next it's United. I am looking forward to it.
"I am now playing for Fenerbahce and I want to do well for my team but of course it will be special to play at home (Old Trafford) in a great stadium with great fans against a great team."
United sit one point behind group leaders Fenerbahce following one win and one defeat.