They have only won one game to date, but remain a tough nut to crack at the Liberty Stadium. Back-to-back derby wins over the Scarlets will have done their confidence the power of good, but this game is more about revenge after the way they slipped to defeat at Franklin's Gardens.
If the Welsh region can beat the Saints then that will probably put an end to Northampton's knock-out aspirations. Then they have to travel to Dublin to face Leinster in round six for another vital game.
The home side will know all about the threat of Saints new strike weapon, George North, who scored his first Heineken Cup try in the famous win over Leinster at the Aviva Stadium in the last round.
"We all know the huge threat that George poses and it was interesting seeing him playing in the centre against Leinster," said Ospreys Welsh international midfield star Ashley Beck.
"If he wants to try to pop up in the midfield at the Liberty then we will be ready for him. Our defence has been good for most of this season and we will be ready for him."
The Ospreys have had a surprising amount of trouble in the front row department this season and head coach Steve Tandy has recognised the need for improvement in that area. Even so, he has left Adam Jones on the bench.
Saints will have Samoan scrum half Kahn Fotuali'i in their starting line-up and he will bring a lot of local knowledge after his time at the Ospreys. The only other change for the side that beat Harlequins last weekend is Tom Wood switching to the No 7 shirt in place of Phil Dowson.
The battle at the breakdown between Justin Tipuric and Wood will be one of the features of the game.
- Northampton triumphed 27-16 against Ospreys in Round 2 - the only previous meeting between the sides in the competition.
- Ospreys are yet to miss a kick at goal this season with Dan Biggar landing all 17 of his attempts.
- Northampton have won more lineouts per game (15.3) than any other side after four rounds.
- Biggar is the joint-top point-scorer in the tournament so far with 55 (Paddy Jackson of Ulster also has 55).