Three juvenile Atlantic tripletailLobotes surinamensiscaught opportunistically in Charleston Harbor (South Carolina, USA) and maintained in captivity for over three months displayed an altered swimming behavior. While no direct causation can be demonstrated herein, fish were infected in their brain by strigeid trematode larvae (metacercariae) ofCardiocephaloides medioconiger, which were identified via ITS2 and 28S ribosomal RNA gene sequencing.Histology showed nonencysted metacercariae within the brain ventricle between the optic tectum and tegmentum, causing distortion of tegmental parenchyma. Aggregates of mononuclear inflammatory cells were in the ventricle adjacent to metacercariae. Metacercarial infection byCardiocephaloides medioconigerhas been reported from the brain and eyes of only two other fish species from the northern US Atlantic coast: the grey mulletMugil cephalusand silversideMenidia menidia,but this identification is problematic and needs molecular verification. Atlantic tripletail is a new report as a second intermediate host forC. medioconigerand South Carolina is a new locality.Cardiocephaloidesspecies in general have a low host specificity and infection byC. medioconigercould propagate to other fishes and affect neighboring natural ecosystems.