Antonio Conte has got the better of former Blues boss Jose Mourinho on both previous occasions, a 4-0 hammering in the league at Stamford Bridge followed by a 1-0 FA Cup exit in March.
Chelsea have not lost to United in any competition since 2012 and any result to continue that run would all but secure the league crown with their remaining games all against teams outside the top six.
Tottenham, again, kick off the weekend action when they host a Bournemouth side effectively clear of relegation, hoping to close the gap at the top to four points for at least 24 hours.
EPL | The Premier League table after 32 matches
Arsenal's pursuit of the top four fell apart in a remarkable 3-0 defeat against Crystal Palace on Monday, and must again wait until after their rivals have played when they travel to face Middlesbrough.
Boro's own plight also looks in vain and will be desperate to pick up points having gone 14 games without a top-flight win.
Palace moved six points clear of the drop zone with that win at Selhurst Park and face a Leicester City side with eyes on their Champions League quarter-final, losing the first leg at Atletico Madrid 1-0. One more win for the Eagles should secure survival for another year.
Talking of one more win, West Ham will now consider themselves safe after beating Swansea City last time out and will be confident of moving further clear of the drop when they travel to bottom-of-the-pile Sunderland.