The defending champions confirmed on Wednesday that the midfielder suffered ligament damage to his right knee in their 2-2 draw against Arsenal on Sunday.
Man City boss Pep Guardiola is now expected to be without one of his key players for the vast majority of the 2024-25 season, harming their chances of claiming a record-extending fifth successive top-flight crown ahead of the likes of Arsenal and Liverpool.
When asked whether Rodri's prolonged absence could be enough to cost City the title, McCoist exclusively told Sports Mole: "Oh I've no doubt. There's no doubt about it because in my opinion, he's the best in the business at what he does.
"Although I did see somebody play against him last week who reckons he's the best in the business at what he does, [Hakan] Calhanoglu in the middle of the park for Inter Milan. And by the way, he did well. But the best in the business at what he does is Rodri. Absolutely fantastic football player.
"Could [the injury] have an effect on the title? Sadly, from City's point of view, for me, it absolutely could.
"It's no coincidence that when you look at Manchester City's results with him and without him. That ain't a coincidence, that's not down to luck, that's down to Rodri and what he does and what he brings to the party and to the team."
McCoist: Rodri is City's "most crucial player"
Man City's record with and without Rodri in their side shows a clear drop-off when the Spaniard is absent, and last season in particular demonstrated his importance to the team, with City not losing a single Premier League match in which he featured, compared to losing all four of those which he missed through suspension.
McCoist therefore believes that the midfielder is even more important to Guardiola's side than star striker Erling Haaland, and believes that the four-time defending champions will struggle to replace their anchor in the middle of the pitch.
"He's probably the most crucial player in that Manchester City team in the respect that I think he's the one that they might find most difficult to replace," the 62-year-old added.
"That's a bit of a statement I'm making with Haaland, Ederson, Dias, boys like that. I mean, it's up for debate, that is, that's another debate in itself, but I'm of the opinion he's probably the one that they'll find hardest to replace.
"I mean, we saw it last year with, was it Jurrien Timber, who got injured with Arsenal? First game or something like that and he was out for the entire season. You know, if you're a player or an ex-player, it's just a nightmare that scenario. So first of all, greatest sympathies to Rodri."
With Rodri in the team, City's only loss last season came against rivals Manchester United in the FA Cup final, but in the Premier League they won 27 and drew seven of his 34 matches.
"If anybody can change things around and be clever with his squad, it's Pep"
Although Guardiola acknowledged the blow of losing such a key player, he spoke positively about the ability of his squad to adapt and overcome setbacks, highlighting how his team won the title in 2023-24 despite missing Kevin De Bruyne and Erling Haaland for months of the season.
McCoist was in agreement, acknowledging that if any club can cope with Rodri's absence, it is Man City: "The one thing they have got is the best squad in the country, if not I think in world football to tell you the truth.
"So they have got other players that can come in and adapt, and if anybody can change things around and be clever with his squad, it's Pep. But it's certainly a problem they could have done without."
Rodri's injury came in the wake of his comments highlighting the physical toll of fixture congestion on players, with the threat of strike action even mooted.
The midfielder featured 61 times for club and country over the course of 2023-24, and the timing of his injury perhaps shows the very real risks associated with such large workloads.
Ilkay Gundogan has operated as a holding midfielder in the past for City, and it would not be surprising if he was selected to fill the void that Rodri's injury has created, while Mateo Kovacic is also a possible replacement.
There is also the possibility that Man City could enter the transfer market in January in search of extra cover for the Spaniard's absence.
However, given that Guardiola's side have failed to win nearly 40% of their Premier League games when Rodri has been absent, some might see the Spaniard's injury as a perfect opportunity for Arsenal to pounce on their title rivals.
Ally McCoist was speaking to Sports Mole on behalf of talkSPORT bet.