The intensification of shrimp farming systems has led to the spreading of a variety of bacterial and viral diseases that continue to plague the shrimp industry worldwide. Efforts to combat these pathogenic organisms include the use of immunostimulants, probiotics, vaccines and antibiotics. Although a few studies have already reported on the effects of various stimuli on shrimp, the effect of antibiotics, particularly on the changes in the shrimp transcriptomic profile have yet to be reported. Here we show that injecting shrimp with oxytetracycline and oxolinic acid alters the expression of genes in the black tiger shrimp, Penaeus monodon, lymphoid organ. These antibiotics, especially oxylinic acid, down-regulated the expression of a few immune-related genes, most notably penaeidin, proPO, clotting protein, profilin and whey acidic protein.