Background: The diagnosis of malignancies and premalignant lesions has been aided by the use of numerous tumour markers and enzyme studies. The present study evaluated total serum creatine phosphokinase and serum lactate dehydrogenase levels in patients with oral cancer and oral leukoplakia. Materials & Methods: Group I comprised of Oral leukoplakia patients, group II had oral cancer patients and healthy controls were kept in group III. 5 mL of venous blood was collected and used for estimation of serum CK and LDH levels using Siemens autoanalyzer. Results: Group I had 22 males and 10 females, group II had 20 males and 12 females and group III had 16 males and 16 females. The mean LDH level in group I was 290.2 IU/L, in group II was 318.4 IU/L and in group III was 145.2 IU/L. The difference was significant (P< 0.05). The mean CPK in group I was 78.2 IU/L, in group II was 70.8 IU/L and in group III was 106.4 IU/L. The difference was significant (P< 0.05). Conclusion: Serum LDH and CK measurement is a simple, non-invasive process that may be employed in patients with OSCC and oral cancer as a biochemical marker.