Introduction: The most challenging environmental situation in commercial poultry production is stress including vaccination, heat stress (summer), cold stress (winter) and drug intake stress. The use of NSAIDs may help to minimize the disease outbreaks in broilers. The gene expression of HSP-70 is an endogenous mechanism by which living cells conform to stress. It is reported that, NSAIDs have ability to produce different HSPs in several species. The prophylactic measures should be implemented to avoid the excessive misuse of antibiotics. Objective: This study was planned to determine the effects of NSAIDs including acetylsalicylic acid (ASA), acetaminophen (APAP) and ibuprofen by short term and prolonged use with different combinations on performance and health indicators in broilers and their association with heat shock protein 70, i.e., to conclude the protected level of NSAID’s use in poultry. Materials and methods: In present experiment, by using completely randomized design (CRD) three subgroups in different combinations of non-steroidal anti-inflammatory drugs (NSAIDs) were given orally via drinking water (DW) from 10th to 32nd day of age of birds. The birds were slaughtered on the 14th and 42nd day of age. In general parameters, including weekly live weight, slaughter weight, carcass weight, clinical signs and behavioral alterations were also accessed in slaughtered birds The blood samples were collected without anticoagulant to study the serum-biochemistry and tissue samples were collected at time of sampling to determine the level of HSP-70 at these stages. Results: The weekly live weight and carcass weight were also showed significant results at higher doses of NSAIDs. The higher doses of NSAIDs were showing severe clinical signs and behavioral alterations including dull feathers, low attraction towards feed and water and loose to watery droppings. The serum biochemical parameters and mRNA gene expression of HSP70 showed significant results according to the dose manner of NSAIDs. Conclusion: Administration of low and medium doses of NSAIDs results in improved body weights. The toxicity due to excess dose of acetaminophen was observed in this research.