Coniglio, 27, had only just returned to the Giants' senior side after spending three-months on the sideline after suffering both a syndesmosis injury and a toe complaint in Round 3.
In his first game back at the level last week, the former top-10 draft pick found the football on 19-occasions during a 26-point loss to the Sydney Swans.
Coniglio has yet to play in a win from four attempts so far in 2021 and has not tasted victory since Round 15 of 2020.
Head coach Leon Cameron explained in a statement issued by the club on Saturday afternoon that the Western Australian would miss the Giants' all important Round 19 clash with Essendon at Metricon Stadium.
“Stephen reported soreness in that toe he had operated on earlier this year,” Cameron said.
“It was obviously a really significant injury, alongside the ankle, so we’re taking a cautious approach and he won’t play this weekend.
“We’ll see how he pulls up over the next few days in terms of his availability for next week.”
Former skipper Callan Ward will replace Coniglio in the side, with impending free-agent Josh Kelly set to captain the club in what is set to be his 150th AFL match.
22-year-old Nick Shipley has joined the squad as an emergency.