Pressure continues to surround Louis van Gaal after his Manchester United tenure sunk to a new low as the embattled side were beaten 2-1 by Midtjylland in the Europa League on Thursday.
Having crashed out of the Champions League in December, United were heavy favourites to see off a Midtjylland team playing their first competitive game in more than two months.
David De Gea was injured in the warm-up and, after Memphis Depay's opener 37 minutes in, replacement goalkeeper Sergio Romero was beaten by Pione Sisto on the stroke of half-time.
With United floundering in the Premier League, Paul Onuachu struck 13 minutes from time to condemn United to their 11th defeat of a miserable campaign.
There was better news for former United captain and birthday boy Gary Neville as Valencia made Europa League history in their 6-0 rout of Rapid Vienna at the Mestalla.
Neville has been under pressure since his appointment in December due to rocky La Liga results but a first-half brace from Santi Mina saw Valencia become the first team to score five first-half goals in the competition.
Aritz Aduriz's stunning second-half strike earned Athletic Bilbao a 1-0 win at Marseille, while holders Sevilla are all but through to the last 16 after beating Ole Gunnar Solskjaer's Molde 3-0.
Last year's semi-finalists Fiorentina have work to do in their tricky tie against Tottenham following a 1-1 draw at the Stadio Artemi Franchi, although Borussia Dortmund made the most of home advantage with a 2-0 win over Porto.
Sporting Lisbon fell to Bayer Leverkusen 1-0 following Ruben Semedo's late dismissal, with Villarreal and Anderlecht beating Napoli and Olympiacos by the same scoreline respectively.
Sergej Milinkovic-Savic ensured Lazio a 1-1 draw at Galatasaray and Sparta Prague edged Krasnodar 1-0, while Saint-Etienne prevailed 3-2 against Basel an 10-man Sporting Braga overcame Sion 2-1.
Bundesliga rivals Schalke and Augsburg played out goalless draws with 10-man Shakhtar Donetsk and Liverpool respectively.