The French side won 2-1 at Anfield and Rafa Benitez's side have lost six of their last seven matches in all competitions.
Furthermore, Steven Gerrard is ruled out and Fernando Torres will play despite not being 100 per cent fit.
The Reds are desperate for a positive result to keep their qualification aspirations alive but it will not be easy at Stade Gerland, with Lyon smelling blood.
Arsenal's assignment looks rather more straightforward as they look to effectively clinch their place in the knockout stages against AZ Alkmaar.
Only an injury-time equaliser denied the Gunners victory in the away encounter in Holland and Arsene Wenger's team are strong favourites to collect another three points. Kieran Gibbs deputises for injured left back Gael Clichy.
Barcelona kick things off away to Rubin Kazan, looking for revenge after their shock Camp Nou defeat, with the game in Russia underway at 5.30pm.
In the same group, under-pressure Inter Milan are in the Ukraine to face Dinamo Kiev while Rangers travel to Unirea Urziceni.
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