Background: This cross-sectional cohort study aimed to assess the associations between the serum uric acid levels and oral leukoplakia (OL), submucous fibrosis (OSMF) and squamous cell carcinoma (OSCC), and to correlate these with the clinical and histopathological features of these lesions. Methods: Fifty-two patients with oral potentially malignant disorders (OPMD) (25 OL and 27 OSMF cases) and 33 OSCC patients with complete clinical and histopathological characteristics were included. A healthy control group was also investigated. The serum uric acid concentration was assessed using the uricase method from a blood sample without hemolysis. Results: The level means of serum uric acid in the OL, OSMF and OSCC patients were 3.86±1.31, 5.65±0.85 and 4.99±1.34 mg/dL, respectively, compared to 5.16±0.97 mg/dL in the healthy controls. Conclusions: The serum uric acid levels were reduced in the OL and OSCC patients but they were increased in the OSMF patients when compared to the healthy controls. No significant differences were seen in the clinical and histopathological features of the OL and OSMF patients. Future studies with larger sample sizes may improve the understanding of the contributory role of uric acid in the risk stratification of OPMDs. Although measuring the serum uric acid level involves a simple and economical assay, the data from this cross-sectional cohort does not support the clinical utility of evaluating the uric acid levels in OPMD and OSCC patients. © Translational Cancer Research. All rights reserved.