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St Kilda suffered the heaviest defeat of Ross Lyon's second coming as coach in a 60-point thrashing from the Western Bulldogs, slipping to a 2-4 record.

Ross Lyon concedes St Kilda failed to cope with the "extreme" physical demands of a tough recent schedule and has challenged his players to prove their 60-point thrashing from the Western Bulldogs was an aberration.

After two interstate fixtures, the Saints fronted up for a third game in 11 days at Marvel Stadium on Thursday night and were run off their feet by the Bulldogs in a 19.10 (124) to 9.10 (64) defeat.

Coach Lyon admitted the testing run of matches had been a concern heading into the round-six contest but stopped short of declaring it unreasonable.

"It's interesting. There's always commercial aspirations of your club and who represents you at that time, and then there's the footy agenda," Lyon said post-match.

"It's the demands of the game ... and we're a really honest team that's trying to improve capability, like the Bulldogs are, to chase the ones that have established themselves.

"It's not an excuse ... but we'll find out. We need to regenerate and get going because we're not playing the way we want to."

St Kilda were saved from their heaviest defeat under Lyon - in either of his two stints at the helm - by a Cooper Sharman goal after the siren.

But it was still their worst loss of the season by some margin, after three previous defeats by a total of 13 points.

It left the Saints with a 2-4 record ahead of a daunting interstate assignment against Port Adelaide in round seven.

"I don't want to make excuses, because I want to give credit to the Bulldogs, but certainly with my group there was no angst after the game," Lyon said.

"But we've got to prove it's an aberration and that there were a lot of mitigating circumstances that really challenged us.

"We'll look to respond, we'll lick our wounds tonight."

St Kilda coughed up seven first-quarter goals to one against the Bulldogs and never got back within 30 points as the deficit swelled to as much as 78 during the third term.

Saints fans headed for the Marvel Stadium exits in their droves long before the final siren.

"I feel for our fans and our members because all they see is the performance, and ultimately that's all we're judged on," Lyon said.

St Kilda spearhead Max King is set to return against Port Adelaide after he missed the Bulldogs clash with a knee injury.