AIM: To determine the differences in levels of systemic C-reactive protein (CRP) in patients with geographic atrophy (GA) and sex-based differences in CRP levels. METHODS: Blood samples from patients with GA and controls were collected in a prospective age-related macular degeneration (AMD) registry from August 2014 to June 2021. AMD was confirmed using multimodal imaging and the Beckman and Consensus of Atrophy Meeting criteria for GA. High-sensitivity serum CRP levels were measured using an automated nephelometer. A non-parametric (rank-based) linear regression model was fit with an interaction between sex and GA. RESULTS: There were 97 GA patients and 139 controls, with females comprising 55% and 66% of each cohort, respectively. There is no difference in CRP between cases and controls, with a median (interquartile range) of 1.2 (0.6-2.6) mg/L in GA patients versus 1.3 (0.8–2.9) mg/L in controls (P=0.52). Although females had higher CRP levels compared to males in both the GA and control groups, this difference did not reach statistical significance after adjustment for multiple comparisons. CONCLUSION: There is no significant difference in systemic CRP levels between GA cases and controls.