Watkins has struggled to produce through two games, dealing with a lingering foot injury.
The third-year wide receiver has the ability to break out, scoring nine touchdowns in 13 game last season, but hasn't sniffed the end zone so far in 2016.
The Bills are expected to feature Watkins more in its offense, following the firing of offensive coordinator Greg Roman. Watkins has just six catches for 63 yards this season.
Before the season, Watkins was seen as a WR2 with WR1 upside. Although his talent hasn't been challenged, his health continues to shackle him from being an elite player at the position. I think this was a good move for the Bills, who started Watkins on a short week in its Thursday Night Football loss to the New York Jets. Giving Watkins some much needed rest might just be all he needs to get back to his imposing Sunday persona and production.
WR Sammy Watkins is out today vs. Cardinals due to foot injury, per source. Marquise Goodwin now expected to... https://t.co/iQBfcAFcd5— Adam Schefter (@AdamSchefter) September 25, 2016
Watkins tweeted Saturday night that he was "ready to go out there and compete at the highest level," but later deleted the message.
CBS Sports' Jason La Canfora reported Saturday that the Bills were "holding out hope" for Watkins to suit up.
Bills still holding out some hope Sammy Watkins can play Sunday depending on how he feels in warmups but it's 50/50 at best— Jason La Canfora (@JasonLaCanfora) September 24, 2016
I don't think any of Watkins' fill-ins are start worthy, going up against the Cardinals' top corner Patrick Peterson and a talented secondary. Marquis Goodwin is expected to start opposite of Robert Woods as Tyrod Taylor's top targets.