The 22nd-placed Millers are four points behind Derby County in 21st, with a game in hand over the Rams, but they are running out of time entering the final straight.
A 1-0 defeat to Brentford on Tuesday night means that safety is now out of Rotherham's hands. Even if they win their final three fixtures – against Blackburn, Luton Town and Cardiff City – they need to hope that Derby slip up against either Swansea City or Sheffield Wednesday.
That does not seem that unlikely considering that Wayne Rooney's side are in freefall, but Rotherham are in poor form themselves and must start picking up points.
The Millers have lost their last five matches, but all by one-goal margins, an indication of how they continue to fight to the very end.
Paul Warne has admitted that the "brutal" schedule, which has seen his team play nine games in 25 days due to Covid outbreaks earlier in the season, has simply caught up with their small squad who are exhausted.
However, Rotherham chairman Tony Stewart has confirmed that the club will stick with Warne at the helm regardless of what happens in the next fortnight.
No side in the Championship has picked up fewer points (18) or conceded more goals (34) at home this season than the Millers, who have lost eight of their last nine games at the New York Stadium.
They will hope that a game against a Blackburn team with nothing to play for presents an opportunity to finally get a win on the board.
Rovers are 15th in the Championship and can go no higher than 12th, while they have lost to other struggling sides Wycombe Wanderers and Sheffield Wednesday in the last month.
However, they produced an emphatic display to win 5-2 against Huddersfield Town last weekend as Adam Armstrong netted his second hat trick of the campaign alongside goals from Ben Brereton and Sam Gallagher.
It was like watching Rovers at the start of the season when they were scoring goals for fun and looked capable of mounting a playoff push; a reminder of how the campaign could have panned out.
However, the reality is that it was just a second victory in 10 games for Tony Mowbray's side, which shows how they have slumped in recent months.
Armstrong scored a 98th-minute winner as Blackburn came from behind to win 2-1 in this season's reverse fixture in December, meaning Rotherham have won just one of the last 10 meetings between the two sides.
Rotherham will make a late decision on Viktor Johansson, who suffered concussion against Barnsley and therefore missed Tuesday's game against Brentford. All concussion protocols must be closely followed in order to assess the goalkeeper's availability.
Matt Crooks will serve the final game of his three-match suspension following his red card against Middlesbrough.
Considering Warne's comments on his players suffering from fatigue, changes are expected for the Millers, with Matthew Olosunde, Shaun MacDonald and Freddie Ladapo among the names who could come into the side.
Blackburn boss Mowbray could name an unchanged team after such a pulsating performance against Huddersfield last weekend.
Ryan Nyambe limped off against the Terriers, but it appeared to only be a knock, and he is expected to be available for the trip to the New York Stadium.
It has been an injury-ravaged season for Daniel Ayala, who has made just nine appearances since signing last September, but he is expected to feature for the Under-23s on Friday night and could make the bench for the final game of the season against Birmingham City.
Rotherham United possible starting lineup:
Blackman; Ihiekwe, Wood, A. MacDonald; Olosunde, S. MacDonald, Wing, Giles; Lindsay; Ladapo, Smith
Blackburn Rovers possible starting lineup:
Kaminski; Nyambe, Lenihan, Harwood-Bellis, Bell; Travis, Evans; Brereton, Rothwell, Gallagher; Armstrong
We say: Rotherham United 2-2 Blackburn Rovers
Ordinarily you might give Rotherham a good chance of winning this game as Blackburn have nothing to play for, but the Millers seem dead on their feet and Rovers are on a confidence high after last weekend; it should be an open affair but ultimately we think that the hosts will not quite get the result they need.