Cisse netted arguably the best double Stamford Bridge has seen in the 2-0 win to keep Newcastle in the hunt to snatch one of the final two Champions League qualifying spots.
Defiant Chelsea caretaker manager Di Matteo said: "It's going to be difficult now for us to reach fourth spot. We'll keep pushing though until it's impossible. We won't give up."
Despite the sensational turnaround in fortunes Di Matteo has overseen since taking charge two months ago, Chelsea have paid the price for failing to beat any of the teams above them in four head-to-head clashes.
But Di Matteo said: "We've lost many points during this season. Looking back over the whole season, that's why we're in the position we are."
The Italian refused to use exhaustion as an excuse, despite his side having played every midweek and weekend since he took charge.
"We've been pushing the players for the last two months and they've responded extremely well," said Di Matteo, who also defended his decision to make six changes, including resting both Juan Mata and Frank Lampard. "Tonight, we have to give credit to Newcastle. They did well and played a very good game against us."
Newcastle boss Alan Pardew was still reeling from Cisse's 25-yard banana shot that sealed victory when he arrived for his post-match press conference.
"An astonishing goal," he said after the Magpies' first league win at Stamford Bridge since 1986.
"We were seeing the game out at 1-0. I thought we'd get home with the goal that we had, but Cisse took a chance. You could see he meant it and he hit it absolutely true. It means so much to win here after 18 attempts."
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