A depleted Manly outfit has risen from the dead to claim a memorable 20-16 comeback victory over fierce NRL rivals the Eels at Parramatta Stadium.

The Sea Eagles played the final 20 minutes without a fit player on the interchange bench and trailed 16-14 when Luke Burt scored and converted on the hour.

But somehow they managed to lift to the occasion with substitute hooker Heath L'Estrange sliding over for the winning try in the 74th minute.

The Sea Eagles lost veteran Steve Menzies (hamstring - fifth minute), winger Michael Bani (neck injury - 40th minute) and lock Luke Williamson (concussion - 60th minute) to injury throughout the match.

Mark Bryant also gallantly played on despite a knee injury.

Yet despite the setbacks, Manly still managed to outscore the Eels four tries to two in front of 14,025 fans to claim their fourth win of the season.

It was a heart-breaking defeat for the Eels, who now have just two wins from their opening six games after starting the NRL season as premiership contenders.

Friday night was also their first game since halfback Tim Smith was granted indefinite leave midweek to overcome his battle with bipolar disorder.

Manly led 10-4 at halftime. And when fullback Brett Stewart crossed just six minutes after the break the visitors looked like they could kick on with the match.

Parramatta had thrown everything at the Sea Eagles defence in the first half without success and Stewart's early try could have easily deflated the home side.

But the under-siege Eels responded, with Nathan Hindmarsh providing a desperate grubber in the 55th minute that Matt Orford fumbled in goal allowing lock Chad Robinson to pounce and score.

Williamson was then sent to Disneyland when attempting a tackle on Eels winger Eric Grothe, prompting Eagles officials to call Bryant back from the change rooms to sit on the empty bench.

Seconds later makeshift five-eighth Feleti Mateo provided a perfect banana kick for Burt to score, the fullback's fourth goal giving the Eels a 16-14 lead.

Manly coach Des Hasler rated the win one of the greatest in the club's history as the side also overcame a massive 7-1 penalty count against them.

Although he couldn't find the right words to compare where the victory stood, he may described where the win came from.

"That is what makes this job so enjoyable, you get experience and be part of a win and it will go down as one of the best wins the club has had," said Hasler.

"It was very courageous. We certainly had some obstacles to overcome, three players out and only one left on the bench who was injured and we were probably on the wrong end of the penalty count.

"We are all very proud of the way they performed tonight against some pretty formidable odds."

Orford said the win was better than the Eagles 52-6 thumping of New Zealand in round three.

"Ten times I would rather have this win than the Warriors (win) any day," said Orford.

"Our middle men played the majority of the game with no changes. That was just guts. It mightn't have been pretty but geez it's a very important two points."

Of the Eagles injury worries winger Bani was the biggest concern after he was rushed to hospital in a brace after a heavy tackle just 15 seconds before half time left him with neck tenderness and a tingling sensation in his fingers.

Eels coach Michael Hagan was also left with a numb feeling after the loss, he was visibly shocked at the result and could barely find the words to explain where his talent-laden side is going so horribly wrong.

"It is probably hard to know how to react to that one," said Hagan after several seconds of stunned silence to open his press conference.

"I think the game was there to be won at the end. We gave ourselves a chance to win the game and I think we lost it more than they won it to be fair.

"Defensively we dead set gave them 16 points in their 20 which I am not very happy about.

"We have got the bye next week, that is a fair starting point (to recover). I don't think I could face up to it again next week with some of the things we're tossing up at the moment.

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