Luton were thrashed 5-0 by Reading on Saturday and are five points from safety, while Barnsley also fell to a heavy loss last time out and are four points off Hull City in 21st.
Nathan Jones's return to Luton had been going well until Saturday's home humbling against Reading, with the Hatters' hopes of survival being severely dented in the process.
Town were unbeaten in six matches either side of the three-month hiatus prior to Reading's visit, and it remains to be seen how they react to such a heavy loss.
The good news for Luton, and indeed Barnsley, is that the majority of the sides in the bottom half also dropped points across the weekend.
Like Luton, Barnsley had also picked up some decent results before losing 4-0 at fellow strugglers Stoke City - a result that saw the Potters climb out of the bottom three.
It means that, with five games remaining, the Tykes are four points adrift of safety and Luton five, so defeat for either side on Tuesday could well kill off their survival hopes.
Playing at Kenilworth Road may suit Barnsley, as it turns out, given that they have won three of their last five away matches - albeit with that loss to Stoke coming last time out.
Luton have failed to win their last three matches on home soil, meanwhile, drawing 1-1 with Stoke and Preston North End before the thumping to Reading.
One thing going in Town's favour is that they have a favourable set of fixtures to conclude the season - compared to Barnsley's, at least - with four of their remaining five games against bottom-half sides.
Luton were also 3-1 winners when they last met Barnsley 11 months ago - their first victory since earning promotion to the Championship.
While that reverse fixture gave the Hatters lift-off in the second tier, defeat on Tuesday could well all but end their stay in the division.
Luton Town's Championship form: DDDWDL
Barnsley's Championship form: LLWDWL
Given just how poor his side were, however, Jones may well revert back to something close to the side that held holders Leeds United to a 1-1 draw earlier in the week.
That could mean a return to the side or Callum McManaman, who scored in the recent draw with Preston.
As for Barnsley, captain Alex Mowatt admitted to being "embarrassed" by the loss to Stoke and changes to the starting lineup seem inevitable.
Luton Town possible starting lineup:
Sluga; Pearson, Carter-Vickers, Bradley, Potts; Mpanzu, Cranie, Tunnicliffe; Brown; Cornick, Collins
Barnsley possible starting lineup:
Walton; Sollbauer, Andersen, Williams; Ludewig, Mowatt, Styles, Ritzmaier; Thomas, Chaplin, Brown
We say: Luton 2-2 Barnsley
Both teams fell to heavy losses last time out and are now in the last chance saloon. A nervy game can be expected at Kenilworth Road on Tuesday and we are expecting the points to be shared - an outcome that will not suit either side.