Rotherham visit Hillsborough on Wednesday night in a game that pits second-bottom at home to third-bottom in the Championship.
Rotherham are five points adrift of safety while Wednesday - who on Monday morning appointed Darren Moore as manager - are six points adrift.
“I don’t think it’s a six-pointer, with our positions we’re both desperate to get a win,” said Warne, whose Millers have lost five games in a row.
“It is a big game, it’s always been a big game, I don’t think it gets much bigger than what it is.
“It’s a game where we have to pick our sharpest, freshest players and try and pick a positive team because we won’t go there to sit behind the ball, we’ll go there and try and get at them and win the football game.
“They’re not in a bad run performance-wise. We’ll have to be at our very best to come away with three points.
“The lads know the enormity of every game. We’ve got 15 left and, being as cliched as I can be, they’re all like cup finals.
“I don’t know if it’s a good or a bad thing that it’s Sheffield Wednesday next. Maybe it’s a good thing.”
Rotherham convincingly beat their near-neighbours 3-0 at the New York Stadium back in October, but Wednesday are on their third different manager since then and Warne feels the events of that evening will have no bearing on preparations for Wednesday night.
“We played well against them and took our chances,” reflected Warne. “In recent weeks, we’ve played well and not taken our chances.
“We’ve beaten them once already but when the whistle blows on Wednesday night that will have no effect on the lads’ psychology.
“It’s all about how well you can start the game and can you impress your style on to theirs? I’d be lying if I said that as I sit here now I’m looking forward to the game.
“It’s a big game but beating them already counts for nothing.”
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