Background: HIV/AIDS remains a major health problem in Sub-Saharan Africa. Co-infection with intestinal parasites has been suggested to worsen the outcome of infection by polarizing the immune response towards Th2. This study investigated the IgE profile in patients with diarrhea and with or without HIV and/or intestinal parasites co-infection at the time of diagnosis. Methods and Materials: A cross-sectional study was conducted among diarrheic patients with and without HIV/ AIDS attending at the outpatient Department of the University of Gondar teaching hospital, in Gondar, Ethiopia. Stool samples were examined using standard parasitological procedures. The presence of HIV antibodies was determined by an enzyme linked immunosorbent assay following the manufacturer’s instruction. Results: Among tested diarrheic patients, 109 (52.9%) of them were seropositive for HIV. Chronic and acute diarrheas were diagnosed in 114(55.3%) and 92(44.7%) of the patients, respectively. Intestinal parasites were detected in 30(27.5%) among HIV seropositive and 36(37.1%) of HIV seronegative diarrheic patients. Diarrhea and marked weight loss were found to be significantly associated with HIV infection (P<0.05). Median IgE concentration found in HIV positive diarrheic patients (618 IU/ml, IQR 107.25-971.25 IU/ml) was not significantly (P>0.05) higher than in HIV negative diarrheic patients (618 IU/ml, IQR 304.50-739 IU/ml). Significantly higher association of median total IgE level was obtained in diarrheic male patients (624 IU/ml, IQR 325.50-857.25 IU/ml) than diarrheic female patients (490 IU/ml, IQR 39-835 IU/ml), P<0.001. Adjusted estimates of the effects of HIV, age, and helminth infection on IgE concentration, estimated using linear regression did not showed significant associations. Conclusion: There was a remarkably elevated IgE response in diarrheic patients irrespective of HIV and/or intestinal parasitic infection. The correlation of IgE levels with parasitic infection with or without HIV co-infection as well the immunological and molecular mechanisms of IgE overproduction and its role in HIV infection needs further investigation.