The present study aimed at evaluating the possible effects of Leucas aspera as immunostimulant on mucosal and serum immunity, as well as on growth and resistance against Streptococcus agalactiae infection in Nile tilapia (Oreochromis niloticus) fingerlings. In a 45 days trial, fish were fed experimental diets containing L. aspera 0 g kg (Diet 1- control), 1 g kg (Diet 2), 2 g kg(Diet 3), 4 g kg (Diet 4) and 8 g kg (Diet 5). The results revealed a significant increase in the specific growth rate (SGR), weight gain (WG), and final weight (FW) in fish fed diet 3 (2 g kg) of L. aspera compared to the control and other supplemented groups (P < 0.05). Also, feeding on diet 3 (2 g kg) of L. aspera enriched diet significantly (P < 0.05) increased lysozyme activities in the serum and mucus, serum peroxidase and phagocytosis activity. However, significant (P < 0.05) increase in mucus peroxidase activity was reported in fish fed diet 4 (4 g kg) and diet 5 (8 g kg) of L. aspera, whereas significantly higher (P < 0.05) alternative complement activity was reported in fish fed diet 2 (1 g kg) of L. aspera. At the end of the experiment, nine fish per replication were selected for a challenge test against S. agalactiae. The dietary supplementation of L. aspera significantly reduced the mortality rate and increased the resistance of Nile tilapia following by challenge with S. agalactiae. The highest post challenge survival of 100% was observed in tilapia fed diet 5 (8 g kg) following by 92.6% of RPS in fish fed diet 4 (4 g kg) and 88.9% in diet 3 (2 g kg), 77.8% in diet 2 (1 g kg) and 74.1% in diet 1(0 g kg).