Background The prognosis of COVID-19 cases that suffer from particular comorbidities is worse. The impact of chronic neurological disorders (CNDs) on the outcome of COVID-19 patients is not clear yet. This study aimed to assess whether CNDs can predict in-hospital mortality or severity in COVID-19 patients. Methods Following a cross-sectional design, all consecutive hospitalized patients with PCR-confirmed COVID-19 who were hospitalized at three centers from February 20th, 2020 to March 20th, 2022, were studied. CND was defined as neurological conditions resulting in permanent disability. Data on demographic and clinical characteristics, COVID-19 severity, treatment, and laboratory findings were evaluated. A multivariate Cox-regression log-rank test was used to assess the primary outcome, which was in-hospital all-cause mortality. The relationship among CND, COVID-19 severity and abnormal laboratory findings was analyzed as a secondary endpoint. Results We studied 7370 cases, 43.6% female, with a mean age of 58.7 years. 1654 (22.4%) patients had one or more CNDs. Patients with CNDs had higher age, were more disabled at baseline, and had more vascular risk factors and comorbidities. The ICU admission rate in CND patients with 59.7% was more frequent than the figure among non-CND patients with 20.3% (p = 0.044). Mortality of those with CND was 43.4%, in comparison with 12.8% in other participants (p = 0.005). Based on the Cox regression analysis, CND could independently predict death (HR 1.198, 95% CI 1.023-3.298, p = 0.003). Conclusion CNDs could independently predict the death and severity of COVID-19. Therefore, early diagnosis of COVID-19 should be considered in CND patients. Highlights