Purpose: Association of neovascular age-related macular degeneration (AMD) with C-reactive protein (CRP) was previously reported, indicating a relation to systemic low-grade inflammation. However, visual impairment limits physical activity, and physical activity modulates CRP levels. Here, we investigated the impact of physical activity on CRP levels in patients with neovascular AMD and control individuals. Subjects and methods: We recruited participants from our outpatient AMD program, and control individuals from non-AMD patients, visitors, and department staff. After initial screening of 191 individuals, we included 98 patients with neovascular AMD and 77 controls. All were screened using digital fundus photography and optical coherence tomography, and interviewed about medical history and physical activity. Venous blood samples were obtained for high-sensitivity CRP. Results: Physically active individuals had lower CRP than physically inactive individuals (P=0.003), and physical activity was associated with lower CRP in patients (P=0.038) and controls (P=0.031). Patients and controls did not differ in percentage physically active (P=0.807) or in overall CRP levels (P=0.394). The independent contribution of physical activity on CRP was confirmed in a multiple regression analysis (P=0.009), in which the presence of neovascular AMD did not contribute significantly (P=0.913). Conclusion: Our findings suggest that elevated CRP levels in patients with neovascular AMD are at least partly explained by physical inactivity. Future studies of systemic inflammation among the visually impaired should include disease-related implications, such as the impact of physical activity.