Fish farming in recirculating aquaculture systems (RAS) has been expanding in the recent years, but the effects of water reuse are not well known. The aim of the present study was to compare the growth parameters, stress response and muscle stress- and growth- related gene expression of rainbow trout (Oncorhynchus mykiss) in open system (OS) versus water reuse system (WRS). For this purpose, young rainbow trout were studied in stocking density of 44 Kg/m³ and loading density of 1 L/min/Kg of fish in an OS (100% make-up water) and WRS (66% reused water) for 60 days. The results showed that water NH₃ concentrations increased significantly in WRS compared to OS. In addition, final body weight in the WRS decreased by 6.5% compared to OS on day 60. No differences were observed between treatments in terms of fish length (total, fork, standard), specific growth rate and condition factor. In contrast, feed conversion ratio increased significantly in WRS respect to OS. Moreover, blood plasma cortisol levels as well as RNA expression of heat shock protein 70 (HSP70) in muscle increased significantly in WRS versus OS. However, no significant changes were found in muscle mRNA levels of insulin-like growth factor-1 (IGF-1) and myosin heavy chain (MHC) between the two treatments. In conclusion, water reuse protocol reduced some growth parameters, and induced measurable stress in fish in a manner not related to the expression of IGF-1 and MHC genes.