Background COVID-19 is known to be associated to potentially fatal neurological complications; therefore, it is essential to understand the risk factors for its development and the impact they have on the outcome of COVID-19 patients. Aims To determine the risk factors for developing fatal neurological complications and their outcome in hospitalized COVID-19 patients. Material and methods Case control study based on hospitalized patients was conducted from July 15th 2021 to December 15th 2021. Cases and controls were COVID-19 confirmed patients with and without severe neurological manifestations. Age, comorbid conditions, vaccination status, Blood Sugar Random (BSR), D-dimers levels, anticoagulation type and dosage were taken as predictors (exposure variables) for developing neurological complications. In the case-only (subgroup) analysis, 28-day mortality were analyzed using the same predictors including admission hypoxemia. Chi square test and regression model were built to calculate OR with 95%CI. Results Among 383 patients (median age, 56 years [IQR, 24–110]; 49.9% men); 95 had neurological complications (cases) and 288 did not (controls). Development of neurological complications among COVID-19 related hospitalizations was significantly associated with old age >71 yrs. (cases, 23.2%; controls, 13.5%; OR, 3.31; 95% CI, 1.28–8.55), presence of diabetes mellitus (37.9% vs. 24%; OR, 1.9; 95% CI, 1.2–3.1), admission hyperglycemia (BSR 351–600 mg/dl), (29.5% vs. 7.6%; OR, 3.11; 95%CI, 1.54–6.33), raised D-dimer levels 5000–10,000 ng/ml (41% vs. 11.8%; OR, 5.2; 95% CI, 3.02–8.9), prophylactic dose anticoagulation (43.2% vs. 28.1%; OR, 1.9; 95%CI, 1.2–3.1), and unvaccinated status of COVID-19 patients (90.5% vs. 75.6%; OR, 3.01; 95% CI, 1.44–6.25). Neurological complications with COVID-19 were associated with increased likelihood of death or invasive mechanical ventilation by day 28 (86.3% vs. 45.1%; OR, 7.66; 95% CI, 4.08–14.4). In case-only analysis (median age, 56 years [IQR, 27,110]; 50.5% women), 67 (70.5%) had CVE, 21 (22.1%) had Encephalitis, and 7 (7.4%) had GBS as neurological manifestations. 28-day mortality among these patients was strongly associated with a lower likelihood of vaccination. (6.1% cases vs. 30.8% controls; OR, .146; 95%CI, .033- .64), being younger 17–45 yrs. (12.2% vs. 46.2%; OR, .162; 95%CI, .045-.58), having no comorbid condition (19.5% vs. 61.5%; OR, .151; 95%CI, .044- .525), having cerebrovascular events and GBS as type of neurological manifestation (76.8% vs.30.8%; OR, 7.46; 95%CI, 2.06–26.96), (2.4% vs. 38.4%; OR, .04; 95%CI, .007- 0.24) respectively, and presence of hypoxemia at admission (91.5% vs. 15.4%; OR, 58.92; 95%CI, 10.83–320.67). Conclusion Old age, presence of Diabetes Mellitus, unvaccinated status of patients, high BSR at admission, high D-dimers, and prophylactic dose anticoagulation were identifies as increased risk factors for developing serious neurological complications among COVID-19 patients. Neurological problems in COVID-19 patients raised death risk 7.6-fold. The most common neurological complication was cerebrovascular events, followed by encephalitis and GBS. Unvaccinated status, cerebrovascular events, and admission hypoxemia are associated with an increased likelihood of 28-day mortality among these patients.