Liverpool's hearts were broken by a cruel last-minute equaliser that has all but ended their Champions League dreams for a traumatic season.
The much-maligned Ryan Babel had scored a wonderful goal with just seven minutes left and if Liverpool could have hung on to that lead they would still have had a realistic chance of reaching the last 16.
But Liverpool's season has been littered with shattering luck and bitter body blows, as well as beach-ball goals.
And when Lisandro struck an equaliser in the final seconds for Lyon - sending them into the last 16 - Liverpool knew their own hopes were left hanging by a thread.
Fiorentina's expected win over Debrecen keeps them firmly in second spot and Liverpool will need more than a miracle now after this devastating blow.
Daniel Agger passed a late fitness test on his back injury to play in this crunch Group E clash in the Stade Gerland, boosting the Anfield club's side who were eventually missing seven senior players as they battled for their European lives.
Fernando Torres was also in the starting line-up, while Alberto Aquilani was on the bench, Andriy Voronin partnering Torres up front.
Lyon made two changes from their side that won at Anfield a fortnight ago. Michel Bastos and Bafetimbi Gomis came in for Ederson and Sidney Govou, who were both in the bench.
At first Torres looked barely able to run, certainly with nothing like his usual mobility.
The occasional sprint when needed was about his limit early on such is the severity of the serious groin injury he is carrying.
Lyon may have been lulled into a false sense of security against the Spanish ace, and when he found a yard of space in the box he almost had Liverpool ahead after 12 just minutes.
Emiliano Insua swung over a cross from the left, and the striker met it first -time eight yards to force a fine point-blank save from Hugo Lloris, who was to deny Liverpool twice more before the break.
Liverpool defended deep and in numbers, desperate not to concede early while Lyon had plenty of possession. They moved the ball around crisply and Bastos tested Jose Reina from 20 yards while the giant Gomis had Liverpool's keeper stretching again with a 25-yarder.
But Liverpool were searching for a breakthrough of their own, and another Insua cross gave Dirk Kuyt the chance of a clever lob, again Lloris needing to be at his best to touch the ball over the bar.
The French side then lost Anthony Reveillere and Miralem Pjanic to leg injuries with Lamine Gassama and Ederson taking their places.
Liverpool's third decent chance of the half came after a foul on Torres deep in his own half.
Javier Mascherano's quick free-kick cleared Lyon's back line and allowed Voronin a clear run at goal. His shot was low, but again Lloris was up to the task, blocking the effort with his legs.
Agger was booked after 33 minutes for blocking Gomis' run on the halfway line, with Lisandro cautioned for a foul on Kuyt a minute later.
Lyon started the second period with a quicker tempo, and Lisandro hooked over an Aly Cissokho cross. The full-back's next cross saw Bastos head over the far angle.
The match was now unbelievably tense, one mistake could ruin a creditable performance by Liverpool.
And Lyon were increasing the pressure to grab the goal that would put them into the last 16.
As Liverpool pressed forward, the gaps were appearing behind them, and Gomis looked increasingly dangerous.
Liverpool's first change came after 67 minutes when Babel replaced Voronin, Torres being left on this time.
Then Lloris made yet another stunning save, turning away Lucas' effort with his left hand with Kuyt following up with an overhead shot that was kicked off the line.
Lyon brought on Govou for Gomis, before Reina had to make his first serious save of the night, blocking Lisandro from close range.
Lisandro got away again after 78 minutes, turning Agger and then firing a curling shot just wide of the far post with Liverpool now playing with four men up front.
Torres' misplaced header gave Bastos another chance to run at Liverpool's defence, his shot being deflected for a corner.
But Liverpool broke from defence after a painful bout of head tennis to get the ball away and grabbed a sensational goal after 83 minutes.
Yossi Benayoun spun the ball out to the left for Babel, who cut inside to unleash a thunderous drive into the top corner from 30 yards, before being engulfed by his team-mates.
Three minutes from the end Torres was finally taken off, David Ngog taking over up front.
But with just seconds left, Liverpool's dream crashed. Lisandro got past Insua in the box and lifted his shot over Reina for the equaliser.