In Vietnam, the growth of black tiger shrimp (Penaeus monodon) aquaculture, has resulted from the expansion of farming areas, adoption of new culture techniques and enhanced level of intensification. The use of pesticides and antibiotics in shrimp farming has increased to prevent and to treat disease. These compounds pose a potential threat to shrimp health, product quality and, ultimately, consumers’health. The present study aimed to assess the effects of the most commonly used antibiotics and pesticides on biomarker responses in black tiger shrimp in order to develop a useful set of biomarkers to assess the health/stress status of shrimp and product safety. In order to fully investigate the utility of such a comprehensive set of biomarkers, their performance in laboratory and field situations was tested. In laboratory conditions, shrimp were fed with medicated feed containing 4g enrofloxacin (quinolone) or furazolidone (nitrofuran)/kg for 7 days, or exposed to three nominal concentrations of endosulfan (0, 0.01, 0.1, 1 µg/L) or deltamethrin (0, 0.001, 0.01, 0.1 µg/L) for 4 days. After treatment, shrimp were decontaminated during 7 days. Results showed that antibiotics cause very small changes in the oxidative stress status of shrimp. In contrast, lipid peroxidation level (LPO) may be a potential discriminating biomarker to assess the stress level in farmed shrimp. Results also showed that 4 days exposure to 0.1 µg/L deltamethrin significantly (p<0.05) increased LPO in gills. However, none pesticide treatment had a significant effect on the activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST). In addition, acetylcholinesterase activity (AChE) can indicate the health status of cultured shrimp exposed to those commonly used pesticides and antibiotics. Muscle AChE activity should be assessed to point out endosulfan or deltamethrin exposure, whereas gill AChE activity impairment could indicate exposure to furazolidone. The interpretation of biomarker data is challenging because natural variation of environmental factors likely influences enzyme activities. A combination of three temperatures (24, 29 and 34oC), two salinities (15 and 25ppt) and the absence or presence of 0.1µg/L deltamethrin was applied on shrimp during 4 days. LPO suggested that shrimp may not be susceptible to this form of oxidative damage by deltamethrin. While, AChE in muscle was strongly inhibited by deltamethrin at all tested temperatures and salinities, indicating that AChE activity could be the most appropriate tested biomarker of deltamethrin exposure. Moreover, due to strong interactions between deltamethrin exposure and temperature and/or salinity, mostly on GPx, tGSH and CAT, those biomarkers are less suitable for pesticides exposure monitoring in the field. It is also important to carry out field studies in order to examine how abiotic and biotic factors can modify the biomarker responses to toxicants relative to those seen in laboratory conditions, where these factors are controlled. In field conditions, for which two different culture systems were distinguished (intensive and improved extensive), enrofloxacin medication caused very small changes in oxidative stress status. However, the type of culture system has a significant impact on basal oxidative stress level. It is concluded that LPO in gills and hepatopancreas, CAT, GPx, GST in gills, and AChE in muscle could be used as biomarkers of general health status and can discriminate between shrimp cultivated in different culture systems. Finally, another part of this study examines the advantages of the use of biomarkers as an early warning system by applying it to different shrimp farming systems. Shrimp sampled from intensive, or converted from rice paddy to intensive shrimp farming or rice shrimp integrated farming are suffering from an oxidative stress in all studied tissues. The present study provides evidence that integrating a set of biomarkers to define the health status of shrimp in different shrimp culture systems can be useful. Our results could be used as a reference to undertake future research aiming to assess the health of shrimp exposed to xenobiotics. Moreover, the set of biomarkers needs further research. These tools can be used for screening and for diagnosis, in trend analyses or for predictive purposes, including risk assessment.