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The Blades currently sit 10 points adrift of the play-off places with just eight matches left to play in the regular season.
Wrexham were replaced in the top six on Wednesday night by Southampton who earned a 1-0 win against Norwich City to climb above the Red Dragons on goal difference.
But with one more match to be played prior to the March international break, Parkinson has called for an "almighty" effort from everyone connected to the club when his side travel to South Yorkshire.
"Ideally we would want Southampton to drop points, but they didn't. But this weekend is about one almighty effort from all the squad, all the staff and all the supporters," he said.
"This game takes us into a two-week break. It's right up there, I feel, in terms of importance of games, not just this season, but since I've been here. I'll always include the supporters in that.
"Bramall Lane is an amazing arena to play at. Their supporters will be vociferously behind the team and I know our supporters are going to play their part.
"As a team and a staff, we've got to be ready to finish this block of games off and bring us back into the last seven games with a great chance."

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