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Objective: The Spanish health system is made up of seventeen regional health systems. Through the official reporting systems, some inconsistencies and differences in case fatality rates between Autonomous Communities (CC.AA.) have been observed. Therefore the objective of this paper is to compare COVID-19 case fatality rates across the Spanish CC.AA. Material and methods: Observational descriptive study. The COVID-19 case fatality rate (CFR) was estimated according to the official records (CFR-PCR+), the daily mortality monitory system (MoMo) record (CFR-Mo), and the seroprevalence study ENE-COVID-19 (Estudio Nacional de sero Epidemiologia Covid-19) according to sex, age group and CC.AA. between March and June 2020. The main objective is to detect whether there are any differences in CFR between Spanish Regions using two different register systems, i. e., the official register of the Ministry of Health and the MoMo. Results: Overall, the CFR-Mo was higher than the CFR-PCR+, 1.59% vs 0.98%. The differences in case fatality rate between both methods were significantly higher in Castilla La Mancha, Castilla y León, Cataluña, and Madrid. The difference between both methods was higher in persons over 74 years of age (CFR-PCR+ 7.5% vs 13.0% for the CFR-Mo) but without statistical significance. There was no correlation of the estimated prevalence of infection with CFR-PCR+, but there was with CFR-Mo (R2 = 0.33). Andalucía presented a SCFR below 1 with both methods, and Asturias had a SCFR higher than 1. Cataluña and Castilla La Mancha presented a SCFR greater than 1 in any scenario of SARS-CoV-2 infection calculated with SCFR-Mo. Conclusions: The PCR+ case fatality rate underestimates the case fatality rate of the SARS-CoV- 2 virus pandemic. It is therefore preferable to consider the MoMo case fatality rate. Significant differences have been observed in the information and registration systems and in the severity of the pandemic between the Spanish CC.AA. Although the infection prevalence correlates with case fatality rate, other factors such as age, comorbidities, and the policies adopted to address the pandemic can explain the differences observed between CC.AA. [ABSTRACT FROM AUTHOR]