Vilakazi has been ruled out of action for the next six months after rupturing an Achilles tendon during a Bafana Bafana camp recently.
While Mosimane feels for 'Vila', he says his unavailability provides an opportunity for someone else to claim a position in the starting line-up.
"It's sad, it's unbelievable. He was getting there for us. He scored against Amazulu, his confidence was up," Mosimane said.
"Ja, it's a professional sport. Football is a professional sport, injuries will be there.
"We will miss him. But contrary for us missing him, it also gives somebody a chance to play.
"Unfortunately he will miss the Champions League."
Meanwhile, Mosimane is confident the Absa Premiership champions, in seventh place on the table with 11 points from seven games, will get stronger as new signings such as Toni Silva, Andile Jali and Mosa Lebusa settle in at Chloorkop.
"We have new players like Toni Silva, Lebohang Maboa, Musa Lebusa, Andile, a lot of new players in the team. It will gel, it will come, it takes time.
"As long as we are winning. I told the boys when I was in Morocco that I want to see the pictures of the players lifting the trophy [Prince Mangosuthu Legacy Cup] in Ulundi [on October 13]. I know it's a friendly but it's a cup. You must lift a cup.
"I told Musa that I want you to win cups because you came here from Ajax [Cape Town] to lift cups.
"Here we lift tophies. We are a cup-winning team, not playing football for hope, football for top eight.
"You must win a cup every year. It's been our motto, it's a slogan and we do that."
Sundowns are set to travel to East London for their next league fixture against Chippa United on Saturday.