Sleep is considered as a physiological regulator in the body. Gamma-aminobutyric acid (GABA) is a neurotransmitter that modulates sleep and affects cardiac functions. We evaluated effects of acute sleep deprivation (SD) on cardiac hemodynamic parameters, expression of pro-inflammatory cytokines, and Heat shock protein (Hsp70), serum level of lactate dehydrogenase (LDH) and prooxidant/antioxidant balance (PAB). Male Wistar rats were bilaterally cannulated in the central nucleus of amygdala (CeA) and saline or bicuculline was injected 24 hours prior to induction of 30 minute ischemia following 120 minute reperfusion. Forty-eight animals were randomly divided into four groups: Control (CONT), bicuculline (BIC), acute SD and bicuculline + acute sleep deprivation (BIC+SD). Animals in SD and BIC+SD groups were put in an aquarium for inducing sleep deprivation. SD attenuated LDH, pro-inflammatory cytokines and PAB; improved cardiac hemodynamic parameters and increased Hsp70 in non-infarcted area as compared to CONT. Administration of bicuculline increased LDH, pro-inflammatory cytokines and PAB, reduced cardiac hemodynamic parameters and Hsp70 as compared to CONT. Furthermore, bicuculline administration prior to acute sleep induction decreased SD effects on LDH, PAB, Hsp70, cardiac hemodynamic parameters and pro-inflammatory cytokines. Induction of SD prior to ischemia/reperfusion induces cardioprotection through suppressing inflammatory responses.