Even if the Falcons win at the Matmut Stadium, they will be still relying on group leaders Toulon to be the victims of a monumental upset away against Italian side Petrarca Padova, otherwise Newcastle's minuscule quarter-final hopes disappear completely.
The Falcons are also injury hit and have been forced to name six front rowers on the bench.
Jimmy Gopperth captains the side from full-back in place of Tom Catterick (hamstring) so Joel Hodgson starts at No 10.
Jeremy Manning, who captained the team in last week's win over Padova, is out with a medial collateral ligament strain so James Fitzpatrick comes into midfield.
Up front, Taiasina Tu'ifua (ankle) is ruled out so Ally Hogg comes into the engine room with Michael Mayhew getting the nod at hooker ahead of Joe Graham who drops to the bench.
New Falcons coach Gary Gold has left team affairs in the hands of Paul Moriarty this weekend.
"I only landed on Tuesday afternoon, we have had one training session since then and it is all in Paul's hands for Saturday," said the South African.
"He did a great job against Padova, the confidence is high and from my end I am just going over to observe."
Lyon Olympique: Lespinas, Ratuvou, Thomas, Raffault, Fatafehi, Sadourny, du Bruyn, Kamga, Testa, Guillamon, Njewel, Dorier, Nzi, Gambetta, Bontinck.
Replacements: Miro, Roux, Toleafoa, Marchois, Tranier, Januarie, Tomamichel, Loursac.
Newcastle: Gopperth, Pasqualin, Eves, Fitzpatrick, Shortland, Hodgson, Pilgrim, Wells, Mayhew, Hall, Hogg, Swinson, Mayhew, Pennycook, Wilson.
Replacements: Graham, Fearn, Murray, Vickers, Welch, McGuigan, Shiells, Chudley.
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