Lazio's Serie A title hopes all but evaporated in a 2-1 loss at relegation-threatened Lecce, which also missed a penalty and had a goal disallowed.
Fabio Lucioni and Khouma Babacar scored for Lecce after Felipe Caicedo had given Lazio an early lead on Tuesday.
Second-place Lazio remained seven points behind Juventus, which played at AC Milan later and could take a huge step towards a ninth successive Serie A title.
Lazio was just a point behind Juventus when the season was halted because of the coronavirus pandemic. It was on a record unbeaten run of 21 straight matches but the capital side has lost three of its five matches since the season resumed.
"The break penalized us, we are not the same as before, especially on a mental level. However, this is not an excuse, but just a fact," Lazio forward Ciro Immobile said.
"But we have to finish the season well, also to not cancel everything good we have done in the last few months."
Lecce moved out of the relegation zone, a point above Genoa, which hosts Napoli on Wednesday.
Lecce thought it had taken the lead after two minutes through Marco Mancosu but it was ruled out for handball in the buildup.
Instead, Lazio took the lead moments later when Lecce goalkeeper Gabriel slipped under pressure from Immobile. He still managed to parry the first Lazio attempt but Caicedo hit the rebound into an empty net.
Lecce leveled on the half hour mark when Babacar was left unmarked, eight yards out, to head in Filippo Falco's cross.
The home side had a great chance to take the lead in first-half stoppage time but Mancosu blasted a penalty over the bar, following handball from Patric.
However, Lecce did go in front two minutes after the break when Lucioni headed in a corner.
Gabriel atoned for his early error with several saves to keep Lecce in front, including stopping Bobby Adekanye's header from point-blank range, four minutes from time.
Lazio's bad night was complete when Patric was sent off for biting Giulio Donati.
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