Background Nipah virus (NiV) infection poses a significant threat to global public health. Understanding its initial acute clinical phase and associated immunological responses may be crucial for assessing prognosis as well as developing effective treatment strategies. Methods: During the 2023 and 2024 NiV outbreaks in Bangladesh, clinical and laboratory data from 15 confirmed cases were collected in this study. Throat swabs and serum samples were tested for viral detection by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and humoral immune response by enzyme-linked immunosorbent assay (ELISA) respectively. Findings: Cases were evenly distributed between genders, with a median age of 18 (0-65) years. The case fatality rate (CFR) for the 15 cases was 80% (12/15), with a median survival duration of 6 (3-16) days since illness onset among the deceased. Of the 12 (80%) primary infection cases, all had a history of raw date palm sap (DPS) consumption within 28 days preceding symptom onset. The median incubation period among primary cases was 11 days (range: 3-19 days), 3 days longer than that of secondary infection cases. Survivors exhibited a longer median incubation period of 13 (11-14) days compared to fatal cases for whom it was 10 (1-19) days. Serum samples from survivors tested by PCR were negative, indicating no evidence of viremia on diagnosis, whereas 92% (10/11) of the fatal cases that could be tested for serology, tested positive with their primary diagnostic sample. Anti-NiV IgM and IgG were detectable as early as the fourth and sixth day post-symptom onset, respectively, and as late as the 34 ^th day. All survivors tested IgG positive on diagnosis compared to only half of fatal cases. Interpretation: The study provides critical insights into the clinical indices, immune response, and viral detection during NiV infection. This could be pivotal in predicting clinical outcomes and guiding treatment strategies for NiV infection. Funding: US CDC, Atlanta