Shaun Williams will miss a period of "months rather than weeks," Millwall boss Neil Harris confirmed after Saturday's 3-1 Sky Bet Championship defeat to Barnsley at The Den.
The Irish midfielder had featured in every League game prior to the loss to The Tykes and recently made his 150th start in a Lions shirt, but Williams is now set to miss the rest of 2017 with the setback.
"Shaun picked up a knee injury in the first-half on Tuesday night, but he continued to see out the game," Harris told iFollow Millwall. "We hope for the best, but it's not looking like good news. He's going to be out for a period of time - months rather than weeks.
"We'll miss him, because he's been a top performer during the start of the season."
Ryan Tunnicliffe replaced Williams in the starting line-up last weekend - his first League start - and the manager praised the summer signing, as well as explaining how Ben Thompson can help add competition in "filling the void" left by the midfielder.
"There's an opportunity for other people [in Shaun's absence]. Ryan Tunnicliffe came in on Saturday and I thought he acquitted himself very well. He's not had a lot of time in a Millwall shirt, so it's going to take him time to learn, but with the break coming up, we can get some good messages into him.
"Ben Thompson has been chomping at the bit, also, on the back of a couple of successful years here. He's a young lad and he is waiting for his opportunity as well. We've certainly got players that can come in and fill the void."
Meanwhile, Harris hopes that striker Tom Elliott can return after the international break to ease The Lions' attacking options.
"Tom's been a big miss for us," he added. "Not just because of his presence and availability, but I've kept playing Steve Morison - who plays with his heart on his sleeve and leads by example - who isn't getting younger.
"Steve needs that respite and support in attack. We'll certainly be a better squad with Tom fit."