United finished sixth in the Premier League last season, meaning they missed out on Champions League football this term and were entered into Friday's draw with Arsenal, who make their return to European competition after a year out.
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This year's competition will see Cristiano Ronaldo make his first appearance in the Europe's second-tier club competition since 2002, when he appeared for Sporting Lisbon against Partizan Belgrade at age 17.
Sheriff will be looking to repeat their giant-killing heroics against United this term, with the Moldovan club having claimed an unlikely 2-1 victory away to Real Madrid in the Champions League last season. Group E will also see a return to Manchester for midfielder David Silva, who joined Sociedad in 2020 after a hugely successful decade at Manchester City.
The draw means Van Nistelrooy will return to face Arsenal after he enjoyed a fierce rivalry during his five-year spell as a player at United, the height of which occurred when he missed a penalty against Arsenal in 2003, a significant event in the north London club's "Invincible" season.
Elsewhere, Jose Mourinho will face off again with Manuel Pellegrini when Conference League winners Roma take on Real Betis in Group C. Mourinho infamously replaced Pellegrini at Madrid in 2010, and the pair have clashed since then, both in LaLiga and when Mourinho's Chelsea pipped Pellegrini's Manchester City to the Premier League title in 2015.
The group stages of this season's Europa League will take place from Sept. 8 to Nov. 3, finishing weeks before the start of the 2022 World Cup in Qatar. The knockout stages will begin on Feb. 16, 2023, with the final scheduled to be held at the Puskas Arena in Budapest, Hungary, on May 31, 2023.
David Moyes' team reached the Europa League semifinals last season but were defeated by eventual winners Eintracht Frankfurt.
Scottish side Hearts have been placed in a tough group with Italian side Fiorentina, Turkey's Istanbul Basaksehir and Latvian side RFS.
Last season's Champions League semifinalists Villarreal are in the same group as Hapoel Beer Sheva, Austria Vienna and Lech Poznan.
GROUP A: Arsenal (England), PSV Eindhoven (Netherlands), Bodo/Glimt (Norway), FC Zurich (Switzerland).
Sept. 8 - FC Zurich (A)
Sept. 15 -PSV Eindhoven (H)
Oct. 6 - Bodo/Glimt (H)
Oct. 13 - Bodo/Glimt (A)
Oct. 27 - PSV Eindhoven (A)
Nov. 3 - FC Zurich (H)
GROUP B: Dynamo Kyiv (Ukraine), Rennes (France), Fenerbahce (Turkey), AEK Larnaca (Cyprus).
GROUP C: AS Roma (Italy), Ludogorets (Bulgaria), Real Betis (Spain), HJK Helsinki (Finland).
GROUP D: SC Braga (Portugal), Malmo (Sweden), Union Berlin (Germany), St Gilloise (Belgium)
GROUP E: Manchester United (England), Real Sociedad (Spain), Sheriff Tiraspol (Moldova), Omonia (Cyprus).
Man United's fixtures:
Sept. 8 - Real Sociedad (H)
Sept. 15 - Sheriff Tiraspol (A)
Oct. 6 - Omonoia (A)
Oct. 13 - Omonoia (H)
Oct. 27 - Sheriff Tiraspol (H)
Nov. 3 - Real Sociedad (A)
GROUP F: Lazio (Italy), Feyenoord (Netherlands), Midtjylland (Denmark), Sturm Graz (Austria).
GROUP G: Olympiakos (Greece), Qarabag (Azerbaijan), SC Freiburg (Germany, Nantes (France).
GROUP H: Red Star Belgrade (Serbia), AS Monaco (France), Ferencvaros (Hungary), Trabzonspor (Turkey).