Merseyside derby rivals Liverpool and Everton will both aim to avoid upsets against lower league opposition when they take on Exeter and Sheffield United in the Carling Cup second round.
Elsewhere, Blackburn host Sheffield Wednesday, Bolton welcome Macclesfield, and Middlesbrough travel to Peterborough.
The rearranged first-round matches between West Ham and Aldershot, and Bristol City and Swindon are also set to take place on Wednesday night.
Kenny Dalglish's Liverpool compete in the second round of the League Cup for the first time since 1999 and Jamie Carragher has described the trip to League One Exeter as 'massive' in the five-time kings of Europe's rebuilding process.
Everton captain Phil Neville has admitted to the negativity which is surrounding the cash-strapped Goodison Park club and they will therefore be desperate for a win against former Premier League rivals Sheffield United.
After two defeats from two league games, Steve Kean is in need of a first win of the season when his Blackburn side take on Sheffield Wednesday at Ewood Park.
Bolton manager Owen Coyle suffered a miserable third-round exit at the hands of former club Burnley in last season's third round. He will as a result want a better challenge in the competition when his team start their campaign against Macclesfield.
Middlesbrough have been impressing the critics so far this campaign and Tony Mowbray will hope for more of the same against Peterborough in the all-Championship game at London Road.
As a consequence of the London riots, West Ham's first-round game against Aldershot was postponed to leave Sam Allardyce's club playing catch-up.
Likewise, Bristol City saw their match versus Paolo Di Canio's Swindon called off due to civil unrest, but they will meet at Ashton Gate.