The 34-year-old striker has scored six Premier League goals on Boxing Day, more than any other current player.
A hat-trick at Old Trafford would draw Defoe level with Robbie Fowler, who holds the record of nine Boxing Day goals.
Premier League top Boxing Day scorers
Defoe is also among the leading all-time scores in the festive period. The Sunderland striker scored twice against Aston Villa on 2 January this year to take his tally for the three PL matches after Christmas to 14.
That return took him up to seventh on the all-time list, within one goal of Frank Lampard and Andrew Cole.
Premier League top Festive period scorers
|Andrew Cole, Frank Lampard||15|
Manchester United are, perhaps not surprisingly, the team to have scored the most Premier League goals on 26 December, with 57.
They are 21 ahead of Liverpool and Tottenham Hotspur, their nearest challengers, with 36 each.
Top-scoring clubs on Boxing Day