The rash of STARI is a red, expanding “bull's-eye” lesion that develops around the site of a lone star tick bite. The rash usually appears within 7 days of tick bite and expands to a diameter of 8 centimeters (3 inches) or more. The rash should not be confused with much smaller areas of redness and discomfort that can occur commonly at the site of any tick bite. Patients may also experience fatigue, headache, fever, and muscle pains. The saliva from lone star ticks can be irritating; redness and discomfort at a bite site does not necessarily indicate an infection.
STARI rashes take many forms.

STARI is diagnosed on the basis of symptoms, geographic location, and possibility of tick bite. Because the  cause of STARI is unknown, no diagnostic blood tests have been developed. Researchers once hypothesized that STARI was caused by the spirochete, Borrelia lonestari; however, further research did not support this idea.

It is not known whether antibiotic treatment is necessary or beneficial for patients with STARI. Nevertheless, because STARI resembles early Lyme disease, physicians will often treat patients with oral antibiotics.