C-reactive protein-to-albumin ratio (CAR) is an independent risk factor in cardiovascular, cerebrovascular, and infectious diseases. Through this study, we investigated the CAR values with respect to the severity and mortality of COVID-19 patients. We performed a systematic review and meta-analysis to retrieve studies that evaluated CAR values upon hospital admission in relation to the severity or mortality of COVID-19 patients. We adopted a random-effect model to calculate the pooled mean difference (MD) and their 95% confidence intervals (CI). Quality assessment was appraised using a Newcastle–Ottawa scale and publication bias was assessed using the Begg-test and funnel plot. We equally performed a subgroup analysis using study location and a sensitivity analysis only with studies with low risk of bias. We analyzed 32 studies (n = 12445). Severe COVID-19 patients had higher on-admission CAR values than non-severe COVID-19 patients (MD: 1.69; 95% CI: 1.35–2.03; p < 0.001; I2 = 89%). Non-survivor patients with COVID-19 had higher CAR values than survivor patients (MD: 2.59; 95% CI: 1.95–3.23; p < 0.001; I2 = 92%). In sensitivity analysis, the relationship remained with a decreasing of heterogeneity for severity (MD: 1.22; 95% CI: 1.03–1.40; p < 0.001; I2 = 13%) and for mortality (MD: 2.99; 95% CI: 2.47–3.51; p < 0.001; I2 = 0%). High CAR values were found in COVID-19 patients who developed severe disease or died.