Tisei, who was a 2012 candidate for Congress, said in a statement that the “timing is simply not right for me.”
He is the second high-profile Republican to pass on the contest, with former GOP Sen. Scott Brown (Mass.) announcing Friday that he would not run.
“I believe it's imperative that the Republican party put forward a strong candidate who can help bring much-needed change to Washington,” he said in his statement. “Unfortunately, the timing is simply not right for me to do so - deeply as I feel about the need to strongly compete in this election.”
“I look forward to continuing my involvement and to supporting strong, principled, independent-minded candidates who may choose to run for this and other offices,” he added.
Two Democratic lawmakers, Reps. Ed Markey (Mass.) and Stephen Lynch (Mass.) have both announced that they will seek Kerry’s former seat, setting up a tough primary fight.
Lynch announced his candidacy last Thursday, but Markey has already lined up the support of many of the state’s Democratic leaders, including an endorsement from Kerry.
But Tisei and Brown’s decisions to opt out of the race have left the GOP nomination wide open.
Republican state Rep. Dan Winslow in a statement said that he was considering whether to enter the race and was weighing "whether there is room in the national Republican Party for a member who is both fiscally prudent and socially tolerant."
Other possible contenders could include local businessman Gabriel Gomez and former GOP presidential nominee Mitt Romney’s wife Ann and son Tagg. A report in the Boston Herald on Saturday said that some Massachusetts Republicans hoped to convince one of the Romneys to contest the race.
Massachusetts Gov. Deval Patrick (D) recently appointed his former chief of staff, William "Mo" Cowan," to fill Kerry's seat until the special election.