The Giallorossi face an uphill battle going into next week's second leg of their Europa League semi-final, after conceding five second half goals at Old Trafford.
Paulo Fonseca's side actually led at half-time, after Lorenzo Pellegrini (from the penalty spot) and Edin Dzeko had combined to offset Bruno Fernandes' opener.
But three first half injuries - to Jordan Veretout, goalkeeper Pau Lopez and Leonardo Spinazzola - would eventually take their toll, as Edinson Cavani (2), Fernandes, Paul Pogba and Mason Greenwood all found the back of the net after the break.
Roma will look back with some frustration at a dubious penalty decision for United when the scoreline was still 3-2, as they began to fade in a second half where those injuries meant further substitutions were impossible.
The two sides face off again next Thursday. Prior to that the side travel to Genoa to face Sampdoria on Sunday evening.
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