The 2-1 reverse made it four defeats in a row, two in the Premier League and two in the Champions League, for Liverpool, their worst run since 1987, when they still finished runners-up to Everton.
With league-leading Manchester United at Anfield on Sunday another defeat, which would be their fifth in the league, will surely guarantee their championship drought extending beyond the 20-year mark.
In the Champions League, Lyon have nine points, Fiorentina six and Liverpool three, leaving the 2005 winners and 2007 runners-up likely to need to win their three remaining games to progress to the knockout stage.
They have done it before but the team turning out at the moment, at least when shorn of Fernando Torres and Steven Gerrard, looks ill equipped to repeat the feat.
Sections of the Anfield crowd booed the team off on Tuesday, disgruntled as much by the performances of the men given the honour of wearing the red shirts as by Cesar Delgado's late winner for Lyon.
Torres missed the game with a groin strain and Gerrard lasted only 25 minutes after going off with a reoccurrence of a similar injury that had ruled him out of last Saturday's loss at Sunderland.
The hosts ended the night with a strike force of David N'Gog and Voronin supported by the ineffective promptings of midfielders Lucas, Fabio Aurelio.
DYNAMIC DUO
Only a few months ago all four would have been lucky to have made Benitez's League Cup squad but the injuries to his dynamic duo combined with the sale of key midfield cog Xabi Alonso have badly exposed the club's lack of depth.
Alonso's 20 million pounds ($32.85 million) replacement Alberto Aquilani has yet to play since his arrival from AS Roma while injury-plagued Voronin has never looked up to the mark in his near three years at Anfield
Asked about the crowd reaction to the removal of Benayoun, who had put Liverpool ahead early on, Benitez said: "The fans know Yossi is a good player but he was a little bit tired. I wanted to use some fresh legs."
"It's a really disappointing outcome," he said of the result "We had too many problems before the game with injuries.
"Now we have to win three games I think. It is the same as it was two years ago. We have done it before and because of that we can do it again."
It might be the same situation but it is not the same team who bounced back from two defeats and a draw by thrashing Besiktas 8-0, Porto 4-1 and Marseille 4-0 away to complete a hugely impressive turnaround.
Gerrard scored in all three of those games, with departed striker Peter Crouch also weighing in with three goals, and Liverpool surged on to the semi-finals.
Gerrard's absence and that of Torres in the last week have merely underlined just how overly reliant Liverpool are on the pair, neither of whom are certain to return against United at the weekend.
"We need to lift ourselves for Sunday, it's something we have to do," Benitez said.
