Background: Environmental, genetic, and immunological factors may play a role in the pathogenesis of age-related macular degeneration (AMD). In an attempt to better understand the pathogenesis of AMD, in this study, we evaluated the serum interferon (IFN) levels in patients with AMD and compared it with persons without AMD. Materials and Methods: In this case–control study, 42 patients with AMD and 42 healthy individuals (without AMD) were enrolled as the case and control groups, respectively. The two groups were matched regarding their age and sex. We classified the case group as dry-type and wet-type AMD. Blood samples were obtained and the serum was collected and frozen at −20°C. Alpha-, beta-, and gamma-IFN levels were measured using the sandwich ELISA method and compared between and within the groups. Results: The mean beta IFN levels in both case and control groups were 46.88 ± 27.25 pg/ml and 34.90 ± 18.81 pg/ml (P = 0.021), respectively. Regarding gamma and alpha IFN, the serum levels were not detectable in most of the patients and no significant difference was detected between the case and control groups. Conclusion: We found that serum beta IFN levels are higher in patients with AMD. This finding may have diagnostic, therapeutic, and prognostic value in AMD patients and can be a beginning for further evaluation.