And with another home game against Worcester Warriors three weeks later, the Ospreys have an ideal chance of reaching the knockout stages again.
Ospreys Coach Sean Holley said: "We're looking forward to defending the EDF Energy Cup and are delighted that the first game will be in front of our home crowd. Harlequins are an exciting team who had a top six finish in the Guinness Premiership last year so it promises to be a great game for all rugby supporters.
"The last two years of the EDF Energy Cup have been very positive experiences for both the Ospreys team and fans, especially last year where we achieved the ultimate prize, lifting the cup in front of our huge travelling support at Twickenham on one of the biggest rugby stages of them all.
"With two home matches at the start of this campaign we'll be looking to mount another serious assault on the trophy and will be doing all we can to keep the trophy firmly where it belongs in Ospreylia."
The EDF Energy Cup, in its fourth year, will again be contested by the 12 Guinness Premiership clubs and the four Welsh Magners League regions.
Three rounds of matches will be played in the four-team group stages at club grounds before the EDF Energy Cup semi-finals and final which will be held on the weekends of March 28 and April 18 respectively - shown live on BBC television.
The BBC will start their coverage with the visit of Guinness Premiership champions London Wasps to Gloucester Rugby in Pool A on Saturday October 4, which also sees Leicester Tigers at Bath Rugby in Pool D and Northampton Saints, back in the Premiership, entertaining Bristol Rugby in Pool D.
EDF Energy Cup Tournament Director Terry Burwell said: "The EDF Energy Cup has provided some fantastic rugby over the last three years and we are anticipating more this season.
"The first weekend alone will provide some exciting match-ups - Bath against Leicester Tigers and Gloucester versus London Wasps, not to mention Saracens against Scarlets and the Blues at Sale Sharks.
"There is a genuine affection for cup rugby among players and supporters, as shown by the 65,000 who turned out for last April's final at Twickenham.
"We are continually grateful to EDF Energy, who have been fantastic supporters of this tournament and domestic rugby at all levels as well as our broadcast partner, the BBC, for their continued support of cup rugby."
Louise Poole, EDF Energy's Director of Sponsorship, said: "With record crowds at the EDF Energy Cup final at Twickenham in April the competition continues to capture the imagination of fans. More tries are scored on average than in any other top club competition, so expect another fantastic season of cup rugby between the best sides in England and Wales."
EDF Energy Cup 2008-2009
|Pool A||Pool B||Pool C||Pool D|
|London Wasps||Bath Rugby||Harlequins||Northampton Saints|
|Gloucester Rugby||Sale Sharks||Worcester Warriors||Saracens|
|Newcastle Falcons||Leicester Tigers||London Irish||