They have won just three of 23 visits to Spain over a span of some 51 years and have tumbled to some chastening defeats during that time. So there's no question Sevilla will prove a tough task on Wednesday for Jose Mourinho's side.
Manchester United have seen their fellow English teams beat all the odds to stand themselves in good stead going into their respective second legs. Manchester City and Liverpool have cruised past Basel and Porto to all but secure their presence in the Champions League quarter-finals whilst Tottenham and Chelsea's ties are finely poised at 2-2 and 1-1, against much tougher opposition.
That leaves just the 'Red Devils' to face off in their Round of 16 first leg, in which they will battle it out with Sevilla at the Ramon Sanchez Pizjuan Stadium on Wednesday, although they will be hoping to not fall foul to this dismal record against Spanish opposition.
In the past 51 years, United have only won three of their 23 visits to Spain (D10, L10), scoring 23 goals while conceding 35.
However, Mourinho's team were victorious in their last oversea trip to the nation, when a Marcus Rashford free-kick gave the Manchester club a 1-0 lead in their Europa League semi-final against Celta Vigo last year. They would go on to lift the trophy.
Apart from that game, the Premier League outfit hadn't faced Spanish opposition since drawing 0-0 with Real Sociedad in the Champions League group stages in 2013-14. Before that they drew 1-1 with Real Madrid in 2012-13 and lost 2-1 to Athletic Bilbao in 2011-12.
Despite the record, United will go into the match as favourites, but it won't be an easy task with Sevilla offering some serious threats among their ranks, in what should be an interesting match-up Wednesday night.