Necrotizing hepatopancreatitis bacterium (NHPB) affects the production of shrimp farms along Latin America. NHPB is one of the main threats to shrimp culture; therefore the defense mechanisms and molecular mediators that act against this bacterium ought to be well understood. The aim of this study was to study the changes in the immune response and the expression of genes coding for proteins of the immune system in the white shrimp, Litopenaeus vannamei, infected with NHPB. Shrimp infected with NHPB and healthy shrimp were maintained under laboratory conditions during 24. d. Haemolymph and hepatopancreas were collected from shrimp every six days. Total hemocyte count (THC), activities of α-2-Macroglobulin (A-2-M), phenoloxidase and total phenoloxidase from haemolymph were monitored. The expression of clottable protein (CP) and lipopolysaccharide & β-glucan binding protein (LGBP) were determined from hepatopancreas, whereas the expression of A-2-M, prophenoloxidase (proPO) and transglutaminase (TGase) was determined from hemocytes. THC showed no significant differences among infected and healthy shrimp at any of the four times. The specific activity of A-2-M significantly decreased on days 18th and 24th post-infection. In the case of the specific activity of total phenoloxidase and phenoloxidase a significant decrease was detected only in day 18 post-infection. CP gene expression decreased at 6th day post-infection, while at 18. days showed an increase of about 2.5-fold. LGBP expression increased in the first six days and at the 24th day post-infection had a drastic decline. The expression of A-2-M showed no significant changes in any of the four times. proPO expression increased more than 4-fold at day 12th post-infection but decreased at 18th day post-infection. TGase expression increased 3.5-fold at day 12th post-infection. The results found in this study suggest an active participation of the proPO system and the clotting reaction against NHP infection, mostly on days 12th and 18th post-infection. © 2013.