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Abstract Our study aimed to explore the association between serum C-reactive protein (CRP) and COVID‐19 mortality. This is a retrospective cohort study of all patients admitted to 4 hospitals within the Montefiore Health System between March 1 and April 16, 2020, with SARS-CoV-2 infection. All-cause mortality were collected in 7 May 2020. The mortality risk was estimated using Cox proportional hazards models. Of the 3545 patients with a median age of 63.7 years, 918 (25.9%) died within the time of cohort data collection after admission. When the CRP was < 15.6 mg/L, the mortality rate increased with an adjusted HR of 1.57 (95% CI 1.30–1.91, P < 0.0001) for every 10 mg/L increment in the CRP. When the CRP was ≥ 15.6 mg/L, the mortality rate increased with an adjusted HR of 1.11 (95% CI 0.99–1.24, P = 0.0819) for every 10 mg/L increment in the CRP. For patients with COVID‐19, the association between the CRP and the mortality risk was curve and had a saturation effect. When the CRP was small, the mortality rate increased significantly with the increase of CRP. When CRP > 15.6 mg/L, with the increase of CRP, the mortality rate increases relatively flat.