While Stade Francais will make the trip to the Kassam Stadium, London Welsh will play their home games against Grenoble and I Cavalieri at the club's spiritual home ground, Old Deer Park in Richmond.
For one of the Exiles' summer acquisitions, Daniel Browne, it will be a chance to lock horns with his former club Grenoble, whom he helped last season reach the Top 14 in what was his second spell with the French club.
"It's exciting and it will be good to catch up with a few guys in the Grenoble team," said Browne, who will get that chance over back-to-back weekends in December.
"Being in the Alps, it's going to be pretty cold in Grenoble in December and they're used to playing in those conditions. That on its own is going to be a big challenge.
"From a team perspective they've recruited really well. The Top 14 is going to be tough, but I think they'll be competitive.
"It's a big challenge for us to go there and win, and to Stade as well. Stade have been one of the best teams in France for a number of years and they've got internationals all over the pitch.
"The priority is to stay in the Premiership, but the Amlin gives us a chance to go overseas and test ourselves against teams of a high standard in other countries. It's a good experience to travel.
"It's a big challenge for us, but a good one."
London Welsh Amlin Challenge Cup Pool 5 Fixtures
Round 1: Saturday 13th October 2012
London Welsh v Stade Francais 3pm*
Kassam Stadium, Oxford
Round 2: Saturday 20th October 2012
Rugby Club I Cavalieri v London Welsh 2pm*
Stadio Enrico Chersoni, Prato
Round 3: Friday 7th December 2012
FC Grenoble Rugby v London Welsh 7:30pm*
Stade Lesdiguières, Grenoble
Round 4: Saturday 15th December 2012
London Welsh v FC Grenoble Rugby 2pm*
Old Deer Park, Richmond
Round 5: 10/11/12/13 January 2013
London Welsh v Rugby Club I Cavalieri
Old Deer Park, Richmond, London
Date and kick-off time TBC after round 4
Round 6: 17/18/19/20 January 2013
Stade Francais v London Welsh
Venue, date and kick-off TBC after round 4
*All Kick-off times local times