The Magpies survived a late Saints charge to triumph 10.10 (70) to 9.10 (64) in a frantic finale to the AFL's Gather Round.
Nick Daicos dominated with a career-high 42 disposals in Sunday's Adelaide Oval thriller as the Pies handed Ross Lyon his first defeat since returning to coach the Saints.
St Kilda trailed by 24 points with just four minutes remaining.
But the Saints kicked three goals in three minutes to sneak within six points with 50 seconds remaining. They attacked again, but couldn't convert another score.
Collingwood backman Murphy will miss the Anzac Day clash against Essendon, who also boast four wins and a loss.
Murphy was concussed in an off-the-ball incident with St Kilda's five-gamer Anthony Caminiti.
Vision shows Murphy forcefully pushing the Saint in the chest and Caminiti responding with a left jab which felled the Magpie.
"I haven't seen the incident but he has obviously been concussed somehow," Collingwood coach Craig McRae said.
St Kilda coach Ross Lyon also said he didn't witness the clash.
"There's cameras everywhere. If there's an incident ... I am sure the processes will kick in," Lyon said.
Magpie McStay was substituted in the second quarter with damage to a finger tendon which may need surgery.
The fresh injury blows came in what McRae described as a "boa constrictor type game".
"It was really hard to find any space on the ground," he said.
Scores were level at quarter-time, Collingwood led by one point at half-time and by six at three quarter-time.
The Pies kicked three consecutive goals in the initial seven minutes of the last quarter, triggered by a goal from Jack Ginnivan in his first AFL game of the year after being banned pre-season for illicit drug use.
Collingwood held the 24-point buffer until the late surge by St Kilda.
"We fought on right to the end," Lyon said.
"We would have stolen it, but that is what you do sometimes in this business."
Brownlow medal favourite Daicos' dazzling display featured eight inside 50s and eight rebound 50s as Lyon and his assistants opted not to tag him.
"Do you lock him down? There's a few things we could have done and maybe we should have, so that's the coaching group that can wear that," Lyon said.
"But I am not sure that was the whole reason (for losing)."
Daicos' brother Josh (30 disposals) was also influential while Bobby Hill kicked three goals and Brodie Mihocek two.
St Kilda youngster Caminiti claimed two majors, as did Brad Crouch (33 disposals) and Jack Higgins, while Jack Sinclair (27), Hunter Clark (26) and Seb Ross (26) were major ball-winners.
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