Background: Immunoglobulin E (IgE) plays an important role in asthma, but a few patients exhibit extremely high levels of serum total IgE. Objective: This study aimed to investigate the profiles of comorbidity and/or complications, severity, and sensitizations in patients with asthma and with a total IgE level > 1000 kU/L. Methods: We retrospectively analyzed 170 patients with asthma and with total IgE levels of >1000 kU/L from the inpatient data base. Available information, including age, gender, body mass index, diagnosis, results of routine blood tests, pulmonary function, fractional exhaled nitric oxide, induced sputum (if any), IgE (both total and specific) tests and medication records were analyzed. Results: In the study subjects, >80% were adults, and the average total IgE level was median (interquartile range) 1438 kU/L (1181-2255 kU/L). Approximately 15% of the subjects had at least one comorbidity and/or complication, and 78.82% of the subjects were positive for at least one allergen. Airway infections (44.71%) and rhinosinusitis (41.18%) accounted for the two most common conditions despite age groups. Total IgE levels did not differ among the subjects with different conditions. Overall, mites had the highest positive rate (59.4%). Serum total IgE levels were positively correlated with house-dust mite specific IgE (sIgE) levels (r = 0.23; p < 0.05), peripheral blood eosinophil counts (r = 0.21; p < 0.01), and the number of confirmed sIgE positivity (r = 0.19; p < 0.01), and optimal scaling analysis showed that asthma severity was associated with Aspergillus fumigatus sIgE levels. Conclusion: In the subjects with asthma and with a total IgE level of >1000 kU/L, the two most common conditions were airway infections and rhinosinusitis, despite sensitization. A. fumigatus sIgE levels were closely associated with total IgE levels and asthma severity.