A collaborative investigation was initiated in rural coastal South Carolina in response to a reported triatomine bite. The eastern conenose bug, Triatoma sanguisuga, was identified and tested for Trypanosoma cruzi. The insect was negative by PCR, and no additional triatomines were found in the vicinity of the home. This is the first published report of a bite from T. sanguisuga in South Carolina despite the fact that triatomine vectors have been documented in the state since the 1850s, and specimens have been collected from homes in the past. Sylvatic T. cruzi reservoirs are common throughout the southeastern United States, and this case brings to light the possibility of human contact with infected triatomines in the state of South Carolina for public health and clinical and entomology professionals.