Indianapolis Colts No. 1 wide receiver T.Y. Hilton aggravated a calf injury in Wednesday’s practice and has been ruled out for Sunday’s home game against the Tennessee Titans.

The team made the announcement Thursday, citing general manager Chris Ballard.

Hilton, a four-time Pro Bowl star, had missed three games with the calf strain before returning on a limited basis in the Colts’ 20-17 loss at Houston last Thursday. He played roughly 25 snaps and caught three passes for 18 yards.

Hilton still leads the Colts with 35 receptions for 378 yards and five TDs.

Not having Hilton is a huge setback for a team short on pass catchers due to injuries entering a critical Sunday matchup of 6-5 AFC South Division rivals vying for a postseason berth. The Colts have lost three of four while the Titans, behind the stellar play of revitalized quarterback Ryan Tannehill, have won four of five.

The Colts were already going to be without wide receiver Devin Funchess, who has yet to return from a fractured clavicle suffered in the season opener, as well as tight end Eric Ebron, who was placed on injured reserve Monday with ankle injuries. The Colts have until next week to decide if Funchess, who signed a one-year deal in the offseason, will be brought back from injured reserve.

Rookie wide receiver Parris Campbell has missed the last three games with a fractured hand that required surgery. He’s practicing on a limited basis this week and is uncertain to play.

Leading rusher Marlon Mack is also out with a fractured hand that required surgery. The Colts, third in in rushing at 144.2 yards per game, have turned to backup Jonathan Williams, who has had back-to-back, 100-yard rushing efforts, the first of his four-year career.

The Colts struggled in the pass game with a limited Hilton as quarterback Jacoby Brissett passed for just 129 yards, including a paltry 4.7 yards per completion, and continually failed to spot open receivers. Brissett is just two games removed from suffering a left MCL knee sprain that caused him to miss one and a half games.

Head coach Frank Reich acknowledged on Wednesday the need to improve yards per catch against the Titans, but that task just became increasingly difficult without Hilton.