Background: OSMF causes iron deficiency as a result of inadequate eating patterns and burning sensations, making it impossible to consume a normal diet and resulting in poor feeding. This study was conducted to assess serum iron levels in subjects having oral submucous fibrosis. Material and methods: 50 OSMF patients with clinical diagnoses and histological confirmation participated in a hospital-based clinical research. Patients in the OSMF group had a habit of chewing areca nuts or one of its commercial preparations, burning sensation, difficulty eating spices, rigid buccal mucosa, vesicle development, ulceration, and blanching of oral mucosa. Patients who chewed solely tobacco, had any systemic issues, were afflicted with a serious illness, or had a habit of chewing areca nuts or one of their commercial preparations without OSMF were eliminated. According to Pindborg's staging, the OSMF group was clinically staged into stages I and II. 50 healthy adults, matched for gender and age, who had no recent serious illnesses or a history of chewing tobacco or areca nuts were included as controls. Results: The study group (OSMF group) comprised of 50 cases with age between 17 and 44 years with a mean age of 26.5 years. The maximum numbers of cases were between 21 and 25 years. The OSMF group showed male predominance with 43 males and 7 females. Mean value of serum iron levels of Control group was 142.27 mcg/dL, whereas that of OSMF group was 63.71 mcg/dL respectively. On comparison of OSMF group with the Control group, OSMF group showed significantly lower levels of serum iron with P < 0.0001. Interstage comparison of OSMF stage II group with the Control group, and OSMF stage II group showed significantly lower levels of serum iron with P < 0.0001. Conclusion: It was concluded that the serum iron levels in subjects having oral submucous fibrosis were significantly lower in comparison to the control group.