Background: Few studies have looked into the impact of hypoglobulinaemia on infectious complications in childhood acute lymphoblastic leukemia (ALL). We conducted this prospective study to analyse the profile of severe infections during maintenance chemotherapy in Indian children and their correlation with serum immunoglobulin levels. Methodology: Children ≤14 years with ALL on maintenance chemotherapy were recruited and serum immunoglobulin levels were measured at the time-of-recruitment in this study conducted between 1st April 2018 and 31st March 2019. Children were followed up for severe infection for a period of 6 months or till completion of treatment whichever was later. Statistical analysis was done to find out risk factors of severe infection including serum immunoglobulin status. Results: We recruited 199 children undergoing maintenance chemotherapy (58, 52, 47, and 42 children in 0-6, 7-12, 13-18 and 19-24 months of maintenance period) and followed them up for a mean (SD) 9.7(2.961) months. 56.8%, 80.4%, and 86.4% children had hypo-IgG, hypo-IgA, and hypo-IgM at the time-of-recruitment. Ninety-one (45.7%) children developed 147 episodes of severe infections of which 54 (59.3%) were respiratory. Univariate analysis showed younger age, female gender and normal IgG group had significantly increased risk of severe infection (P=0.024, 0.007, 0.049, respectively), in multivariate analysis female gender had significantly increased risk of severe infection (P=0.025). Conclusion: Significant proportion of Indian children on ALL maintenance chemotherapy developed severe infection and hypoglobulinaemia. However, hypoglobulinaemia did not significantly increase the risk of severe infection. Younger children and female gender had significantly increased risk of severe infection during maintenance.