Tuesday night will see nine Premier League sides in action in the third round of the Capital One Cup, while Crawley and MK Dons are among those in search of scalps.
In-form Everton are among the top-flight clubs involved in Tuesday's action and they will be keen to continue their impressive start to the season when they travel to Elland Road to take on Leeds, live on Sky Sports 2HD.
Reigning Premier League champions Manchester City host Aston Villa, who have struggled to get a grip on the season so far and will be looking to turn that around with an upset at the Etihad Stadium.
Two other top-flight clubs who are set to collide are West Ham and Wigan, with the Latics out to end the Hammers' unbeaten home record at Upton Park this season.
Crawley have carried the momentum of their promotion-winning campaign last season into League One but suffered defeat at the weekend and will be keen to bounce back by claiming a scalp of Premier League side Swansea at home.
Another third tier side looking to cause upset are MK Dons, who host top-flight opponents Sunderland.
Current league leaders Chelsea entertain Championship visitors Wolves at Stamford Bridge fresh from their last-gasp victory over Stoke at the weekend.
Sheffield Wednesday have struggled on their return to the Championship and will be looking to recover from four defeats on the bounce when they travel to St Mary's stadium to take on Southampton, who claimed their first Premier League win of the season against Villa on Saturday.
League One Swindon also take on higher-league opposition in second-tier Burnley after knocking Stoke out of the tournament in the previous round.
Another third tier side taking on a club in the division above are Preston North End, who will bid to upset Middlesbrough at Deepdale.
Bradford and Burton Albion will battle to become the only League Two side left standing in the competition as they go head-to-head after both making promising starts to the season.