Objective: To estimate and compare the levels of serum copper and iron among subjects with oral submucous fibrosis (OSMF) of different clinical stages and healthy controls. Study Design: Study sample comprised of 50 patients clinically diagnosed with OSMF and 50 healthy controls who were matched for age and gender. OSMF patients were categorised by clinical staging. Serum estimation of copper and iron was done using atomic absorbtion spectrophotometry. Results: Mean copper and iron level differed significantly (p<0.000) between the patients and controls with patients exhibiting higher copper (134.1±20.16) and lower iron (114.78±23.47) levels in contrast to controls who presented lower copper (114.8±12.36) and higher iron (130.86±31.01) levels in serum. There was a definite trend as (P<0.0001) with cases having the lesion in faucial bands (1st stage) exhibiting the lowest serum copper and those in stage 3 (faucial, labial and buccal bands) presenting the highest copper levels in serum. Conclusions: Copper level increased and iron level decreased in study group in comparison to healthy controls. Copper level increased as clinical stage of oral submucous fibrosis increased.