The DUP will have seven days from Middleton’s resignation on Friday to announce his replacement.
DUP leader Gavin Robinson said his party colleague had been a “consistent voice for unionism in Foyle” and that he deeply regrets his departure.
He said: “As the sole unionist MLA in Foyle, Gary Middleton has been a dedicated and steadfast servant to people across the city of Londonderry and surrounding areas.
“In being such a clear and consistent voice for unionism in Foyle, Gary has at times faced threats from republicans.
“That pressure never silenced him nor deterred him, he continued to stand firm for his constituents and his principles.”
Robinson added: “Gary’s focus must now be on his recovery, and he will have the support of colleagues, both inside and outside our ranks, on his journey.”