Newcastle disease remains a major concern to the poultry industry; however, it can be managed with effective vaccination programs. The main objective of this study was to evaluate the effect of 2 1× doses of live LaSota strain Newcastle disease virus (NDV) vaccine administered oculo-nasally on d one and 21 on development of humoral and cell-mediated immune response in broilers, and to compare different immunization schedules. Two experiments were conducted. In Experiment I (n = 320), Ross 308 birds were randomly assigned to an unvaccinated control group or vaccinated treatment. [Both treatments consisted of 4 pens per treatment and 40 birds per pen]. At d one, live NDV LaSota strain vaccine was used as a primary immunization to evaluate its impact on adaptive immunity. No substantial NDV-specific humoral immune response was established. Body weights were significantly higher (P < 0.05) in the vaccinated birds on d 4 and 7. Spleen index of the vaccinated birds was significantly (P < 0.05) lower at d 28 and 35. Flow cytometry showed reduced levels of peripheral and splenic B and T lymphocytes. Interferon gamma secreted by splenocytes and in circulation was measured; the results showed a reduced expression post-secondary immunization. In Experiment II (n = 180), the role of maternal antibodies and primary vaccination at d one was evaluated using 3 vaccination protocols. Protocol 1 used live B1 strain as primary immunization, whereas protocol 2 used live LaSota strain. Protocol 3 used live LaSota strain after maternal antibodies had decayed. Protocol 3 resulted in the highest NDV-titer level during the trial. Protocol 2 had the lowest NDV titer. Feed conversion was significantly higher (P < 0.05) in protocol 3 compared to 1 and 2. Overall, the results indicate that the use of live LaSota strain NDV vaccine as primary immunization at d one has a detrimental effect on the development of adaptive immunity in broilers; however, its use after the level of maternal antibodies decays results in a robust antigen-specific humoral immune response.