Understanding how animals cope with large thermal fluctuations is critical to safeguard species in a changing climate. It has been suggested that if the rate of evolutionary or plastic responses lag behind the rate of climate change, there could be local extinction due to limitations in physiological capacities compared to the environmental variation (Chown et al., 2010). Here, we investigated key markers of the stress response in Atlantic salmon to determine how fish physiology responded to distinct warming scenarios with different nighttime temperatures. If high nighttime temperatures resulted in physiological stress, we would expect that the warmest (22–27°C) treatment would elicit the most obvious signs of cellular and metabolic disturbance. However, this was not the case as different Tmin thermal scenarios had little effect on our dependent variables. These findings lead us to reject the hypothesis that environmentally relevant nighttime temperature is a principal driver in the ability of Atlantic salmon to tolerate multi-day thermal events at, or near, critical temperatures. With future climate change scenarios predicting an increase in thermal extremes and increases in diel thermal minima, it is likely that physiologically important thresholds will be surpassed more frequently. Current regulations regarding recreational angling close the Miramichi River when T ≥ 20°C for two consecutive nights (DFO, 2012). Our results suggest that these regulations be revisited given that the overall effects of ‘warm nights’, at least within the temperature ranges tested here, do not appear to be a critical factor influencing Atlantic salmon. We do show that environmentally relevant diel thermal cycles up to 27°C are stressful for these fish; thus, management decisions should focus on ecologically grounded and relevant simulations of thermal stress and pay attention to maximum temperatures and ΔT. While turning down the temperature of the planet is not an option, an understanding of such biological responses to warming water temperatures will inform the design of effective habitat management strategies to ensure the availability of cool water refugia, protecting Atlantic salmon during these inevitable thermal challenges.