But it could give Republicans a boost in confidence as they struggle to advance health and tax legislation that has been bogged down by infighting and investigations into whether Trump's campaign colluded with Russian Federation in last year's presidential election.
In her victory speech, Handel even gave "a special thanks to the president of United States of America" as the crowd went wild chanting Trump's name.
Democrats raised and spent $23 million in favor of Ossoff's bid against former Georgia Secretary of State Karen Handel, and a combined $50 million was spent in the race overall. But Democrats also had some good luck in 2006 that will be hard to duplicate: There were a half dozen safely Republican districts where the incumbent succumbed to scandal or indictment, including the Tom DeLay, a House majority leader.
"Democrats Demoralized", said an opinion piece in Wednesday's New York Times: "Jon Ossoff's defeat in Georgia will test the party's spirit and its strategy", Frank Bruni wrote. The race-which has garnered national attention and record breaking fundraising-closed out Tuesday night with Handel receiving more than 51 percent of the vote to Ossoff's 48 percent, according to unofficial results posted Wednesday morning.
"When was the last time you heard us talk about those people?"
"We have a lot work to do", Handel said.
Her win marked an impressive rebound from polling that showed her narrowly trailing her rival as the vote approached, and signalled that Republican disillusionment about Trump was not as deep as Democrats were counting on.
The Republican victory - the fourth special election won by the party this year - has generated renewed momentum for the party's long-awaited plan to repeal and replace Obamacare, with Senate Republicans due to unveil their own proposal for the American Health Care Act on Thursday.
Handel is the latest in a line of Republicans who have represented the Georgia 6th since 1979, beginning with Newt Gingrich, who would become House speaker.
Handel will be the only woman in the current 16-member Georgia congressional delegation, and the seventh woman ever sent to Congress from the state.