Warren Gatland's young side host their first fixture still reeling from the recent bombshell - delivered just a couple of hours before the final squad announcement - that jet-heeled Gloucester wing Louis Rees-Zammit would be leaving rugby union with immediate effect in order to pursue his dream of playing in the NFL.
The shock news came as a real blow to their preparations for the tournament, with Wales now trying to find their way into a new era without vastly-experienced old heads such as Alun Wyn Jones, Dan Biggar, Leigh Halfpenny, Justin Tipuric and Rhys Webb, who have all now retired from international rugby.
The injury bug has bitten hard again, with captain Jac Morgan undergoing knee surgery in December and 21-year-old Exeter lock Dafydd Jenkins named as his replacement instead - Wales' youngest skipper since Gareth Edwards in 1968.
Wales put a tough 2023 behind them to reach the quarter-finals of the World Cup in France in the autumn, though will still be ruing the gutting late nature of their eventual defeat by Argentina.
They will be desperate to improve on a woeful Six Nations campaign last year that included just one solitary win, over Italy, and a fifth-place finish, starting against an unpredictable Scotland team who finished behind only Grand Slam winners Ireland and France 12 months ago, winning their first two games for the first time in the modern era - including against England at Twickenham - before failing to maintain their form thereafter.
A battling double-header against France in the summer was followed by Gregor Townsend's men failing to get out of a tough World Cup pool after losses to eventual winners South Africa and Ireland, delivering a battling performance against the former but a complete worrying washout versus the latter.
Wales vs Scotland date, kick-off time and venue
Wales vs Scotland takes place today, Saturday February 3, 2024, with kick-off scheduled for 4:45pm GMT.
The match will be hosted at the Principality Stadium in Cardiff.
How to watch Wales vs Scotland
TV channel: In the UK, Wales vs Scotland is being shown live and free-to-air on BBC One, with coverage starting at 4pm.
You can also watch it live on Welsh-language channel S4C.
Live stream: A live stream can also be accessed for free online via the BBC Sport website and BBC iPlayer.
Wales vs Scotland team news
As mentioned, Wales are without Rees-Zammit due to his shock American football switch, while Morgan and former fellow co-captain Dewi Lake are both sidelined along with the likes of Taulupe Faletau, Christ Tshiunza, Taine Plumtree and now George North, who has a shoulder issue as Owen Watkin lines up with Nick Tompkins in the centres.
There are five uncapped players in Gatland's tournament squad in Cardiff quartet Cameron Winnett, Evan Lloyd, Alex Mann and Mackenzie Martin, plus Bath prop Archie Griffin, with Winnett handed his Test debut at full-back on Saturday.
Scotland have not been immune from injuries themselves, with experienced tighthead WP Nel ruled out with a neck strain and Gloucester fly-half Adam Hastings also out as Javan Sebastian and Ross Thompson were drafted in as late replacements. Ollie Smith is also out and Grant Gilchrist suspended.
Uncapped props Elliot Millar-Mills and Alec Hepburn will both make their first international appearances off the bench against Wales.
Glasgow flanker Rory Darge - named as a Scotland co-captain alongside star fly-half Finn Russell - is closing in on his return from a knee injury, but will not play any part this weekend.
Scrum-half Ben White is fit though after a shoulder issue suffered on club duty for Toulon against La Rochelle last weekend.
Blair Kinghorn is also now out injured, meaning Kyle Rowe makes his first Scotland start at full-back.
Wales vs Scotland lineups
Wales XV: Winnett; Dyer, Watkin, Tompkins, Adams; Costelow, G Davies; Domachowski, Elias, Brown; D Jenkins (c), Beard; Botham, Reffell, Wainwright
Replacements: Dee, Mathias, Assiratti, Teddy Williams, Mann, Tomos Williams, I Lloyd, Grady
Scotland XV: Rowe; Steyn, Jones, Tuipulotu, Van der Merwe; Russell, White; Schoeman, Turner, Z Fagerson; R Gray, Cummings; Crosbie, Ritchie, M Fagerson
Replacements: Ashman, Hepburn, Millar-Mills, Skinner, Dempsey, Horne, Healy, Redpath
Wales vs Scotland head to head (h2h) history and results
Scotland ran out 35-7 winners over wretched Wales at Murrayfield last year, with their last victory on Welsh soil coming in Llanelli in the Covid year of 2020.
However, they have not won in Cardiff for some 22 years now, losing on all of their last 10 visits.
Wales wins: 75
Scotland wins: 51
Wales vs Scotland prediction
Scotland's record in Cardiff is absolutely paltry - indeed, head coach Townsend was in the starting side the last time they won at the then Millennium Stadium all the way back in 2002.
But we fancy them to clear that hurdle here against an inexperienced Wales team lacking leaders and get off to an impressive winning start ahead of the daunting visit of France to Murrayfield in round two.
Scotland to win, by seven points.
Wales vs Scotland match odds
Wales to win: 17/10
Scotland to win: 1/2
Odds via Betfair (subject to change).