West Ham's home meeting with Millwall is the pick of the ties in the second round of the Carling Cup on Tuesday night.
The Hammers welcome their London rivals to Upton Park for what promises to be a fiery contest on the field backed by passionate and vociferous fans in the stands.
Several Premier League clubs will tackle lower league opposition and must weigh up the benefits of resting key players against the threat of suffering an early exit.
Burnley were the Carling Cup giant-killers last season as they claimed a series of Premier League scalps, but they are now in the sights of League One Hartlepool following their elevation to the top-flight.
Blackburn and Bolton have suffered back-to-back defeats in their opening two Premier League outings and need to kick-start their seasons with respective trips to Gillingham and Tranmere.
Portsmouth are floundering at the foot of England's elite division after three successive reverses and are badly in need of a confidence boost when they tackle League Two Hereford at Fratton Park.
Hull City and Wolves have the benefit of home advantage for their showdowns against League One sides Southend and Swindon.
Birmingham and Southampton met in the Championship last term, but their fortunes are now markedly different after promotion and relegation, with League One Saints welcoming the Premier League new-boys to St Mary's.
Middlesbrough have made a solid start to life in the second tier and will be keen to continue their unbeaten start at Nottingham Forest, while Championship strugglers Peterborough and Ipswich meet at London Road.
There are three more all Championship ties with Preston tackling Leicester, Reading up against Barnsley and Swansea playing host to Scunthorpe.
League Two duo Port Vale and Accrington have the chance to cause upsets as they come up against Sheffield Wednesday and QPR.
Leeds United, who reached the final of the League Cup back in 1996, are up against Watford at Elland Road, with the Hornets' last meeting against the West Yorkshire club their 3-0 success in the Championship play-off final in May 2006.