Paul Nuttall's office in Hanley, Stoke-On-Trent, appears to be defaced with red graffiti.
The Ukip leader and Stoke-On-Trent Central by-election candidate lost out to Labour candidate Gareth Snell by 2,620 votes on Friday.
ITV News Political Correspondent Carl Dinnen said Ukip would be "very disappointed" with the defeat.
"They thought they would run Labour much, much closer. It was a reasonably substantial loss", he added.
The vandalism comes days after Mr Nuttall apologised after he faced a storm of criticism over website posts that wrongly claimed he lost "close personal friends" at the Hillsborough disaster.
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