Portsmouth begin their Carling Cup campaign with a trip to Prenton Park, home of Tranmere Rovers, who famously went on a cup run in 2001, knocking out Southampton on the way.
Tranmere Rovers manager Brian Little said of the tie: "It's a great game for us and I am very pleased we are at home. "This competition gives Premiership clubs such as Portsmouth the chance to win a trophy so it's a massive game for them to win as well".
Tranmere Rovers defeated League Two new boys Shrewsbury Town 2-1 in the first round to earn the right to face Portsmouth.