New Manchester United signing Alexis Sanchez could make his debut against Yeovil Town in the FA Cup fourth round on Friday, while Tottenham Hotspur will be out to avoid an upset against another fourth-tier side in Newport County a day later.
Having missed Arsenal’s third-round defeat at Nottingham Forest, United’s new No 7 avoided being cup-tied for the remainder of this season’s competition, and could feature at Huish Park in Jose Mourinho’s 100th match in charge.
The trip to Somerset will be familiar to some United fans after the 12-time FA Cup winners, under former manager Louis van Gaal, laboured to a 2-0 success over Yeovil in the third round in January 2015.
Having been pushed all the way by Bristol City in their League Cup semi-final second leg victory earlier this week, Premier League leaders Manchester City face another Championship side in Cardiff City on Sunday.
The Welsh side are unbeaten in their last four matches in all competitions, and have previous against a top-flight City side, having knocked them out in the fourth round of the FA Cup in 1994, while in England’s third-tier.
Another upset could take place at Rodney Parade on Saturday as League Two outfit Newport County welcome Tottenham to south Wales.
This is the first time these two teams have faced each other since consecutive FA Cup meetings in 1959 and 1960, with Spurs winning both games, scoring four in each.
It is Yeovil, however, who could really claim the biggest scalp.
United have progressed in each of their last 16 FA Cup ties against teams from the fourth-tier or lower, keeping clean-sheets in each of their last 11.
Trailing City in the league by 12 points, another Premier League title appears to be out of reach for United.
Therefore, Mourinho is unlikely to take too many risks with his starting XI as he chases arguably his best chance of silverware this season.
Elsewhere, West Ham United take on in-form League One side Wigan Athletic. Among sides in the top four tiers of England, only City (29) and United (24) have won more competitive games this season than Wigan (23).
Other Premier League sides in action against underdog opposition are Leicester City at Peterborough United and Swansea City at Notts County.