Bristol City defender Rob Atkinson is set to miss around 10 weeks after sustaining a "really bad" ankle injury during their 2-1 win against Blackburn Rovers on Tuesday.
The 27-year-old was substituted at half-time at Ewood Park following a heavy tackle.
Atkinson's absence follows fellow defender Rob Dickie being ruled out for 10 weeks with a hamstring injury, while Luke McNally is unlikely to feature this season after a setback in his recovery from ACL injury.
It means head coach Gerhard Struber has been left with one fit specialist senior centre-back in Noah Eile, who has only played 181 Championship minutes since arriving from New York Red Bulls on deadline day earlier this month.
Full-backs George Tanner and Cam Pring have been used regularly in a back three but the Robins do now look very light in defence.
"It's really bad news," boss Gerhard Struber said in his press conference before Friday's game against Watford (20:00 GMT). "This a really big hit for us.
"When you lose a player like Rob Atkinson or Rob Dickie, it's not so easy to say that we have the next.
"We will miss him but at the same time, it's a big chance for other players."
In positive news for the squad, right-back Ross McCrorie is "ready to come back" after missing three games with a concussion sustained during training. The Scotland international has previously deputised at centre-back on occasions.
However, midfielder Joe Williams is also set to miss a long period with his latest hamstring issue, though Struber is unsure on a timeline at present.
The Austrian has opened up the possibility of entering the free agent market - but whether anyone will be brought in or not remains to be seen.
Struber added: "We are looking what is maybe available. It is not easy to find one but right now we are watching."