The Owls are well adrift at the bottom before a ball has even been kicked, with this a tricky test to begin the season against last year's playoff semi-finalists.
Wednesday have been punished by an independent disciplinary panel for breaking spending rules, though some will argue that the deduction should have kicked in last season.
That would have sent the Yorkshire club down to the third tier given that they finished just eight points above the drop, but as it is they now have a realistic shot of staying up.
For that to happen, Garry Monk's side have to make a fast start to the campaign or else they will soon leave themselves with too much work to do.
Monk's men have a tough set of fixtures to kick things off, though, with this trip to Cardiff followed by games against Watford and Bristol City in their first four outings.
Worryingly for Wednesday, they are winless in their last nine away league matches against Cardiff, with each of the last four ending level.
However, while City enjoyed a positive campaign overall last time out, their preparations for this new season have been pretty disastrous.
After losing 3-0 to Northampton Town in the first round of the EFL Cup, they were forced to release winger Nathaniel Mendez-Laing on Wednesday for a breach of contract.
Promotion will be the aim for Cardiff after coming so close last time out, but that will not be possible if they repeat last week's performance at Sixfields.
Cardiff started last season under Neil Warnock, of course, and they kicked off their campaign with a 3-2 loss at Wigan Athletic.
Indeed, the Welsh side have lost their last two season openers in the Championship - not since between 1982 and 1984 have they lost three on the spin.
After plenty of upheaval off the field, both teams will now be keen for Saturday's fixture to come around.
Cardiff City form (all competitions): L
Sheffield Wednesday form (all competitions): W
As well as likely being without Tomlin, who has been directly involved in eight goals in 12 league appearances against Wednesday, Cardiff are also ruing the loss of midfielder Joe Ralls.
Mendez-Laing is no longer in the picture, but Harris can now call upon Liverpool loanee Sheyi Ojo in a like-for-like change.
Kieffer Moore is also in contention for his competitive debut this weekend after missing the Northampton loss due to being away on international duty with Wales.
As for Wednesday, they were without four first-team players for their EFL Cup first-round tie with Walsall, which they won on penalties after a goalless draw in normal time.
Cardiff possible starting lineup:
Smithies; Osei-Tutu, Morrison, Nelson, Bennett; Pack, Bacuna, Vaulks; Murphy, Moore; Hoilett
Sheffield Wednesday possible starting lineup:
Wildsmith; Iorfa, Lees, Borner; Palmer, Luongo, Bannan, Harris; Brown; Rhodes, Windass
We say: Cardiff City 2-1 Sheffield Wednesday
Wednesday will be desperate to start making inroads after being hit with a 12-point deduction, but this is one of the toughest fixtures they could have asked for to kick things off.
Cardiff had the fourth best home record in the Championship last season, losing just three of their 23 matches, and we can see them edging this contest.