Snake fungal disease (SFD) is an emerging disease caused by the fungal pathogen, Ophidiomyces ophiodiicola. Clinical signs of SFD include dermal lesions, including regional and local edema, crusts, and ulcers. Snake fungal disease is widespread in the Eastern United States, yet there are limited data on how clinical signs of SFD compare with laboratory diagnostics. We compared two sampling methods for O. ophiodiicola, scale clip collection and swabbing, to evaluate whether collection method impacted the results of polymerase chain reaction (PCR). In addition, we evaluated the use of clinical signs to predict the presence of O. ophiodiicola across seasons, snake habitat affiliation (aquatic or terrestrial) and study sites. We found no significant difference in PCR results between sampling methods. Clinical signs were a strong predictor of O. ophiodiicola presence in spring and summer seasons. Snakes occupying terrestrial environments had a lower overall probability of testing positive for O. ophiodiicolacompared to snakes occupying aquatic environments. Although our study indicates that both clinical signs of SFD and prevalence of O. ophiodiicola vary seasonally and based on habitat preferences of the host, our analysis suggests that clinical signs can serve as a reliable indicator of O. ophiodiicola presence, especially during spring and summer.