The mean stress effect on the fatigue life of 304L austenitic steel was evaluated at 300 °C in air and pressurized water reactor (PWR) environments. Uniaxial tests were performed in strain-control and load-control modes, with zero mean stress and a positive mean stress of 50 MPa. A specific procedure was used for the strain-controlled experiments to maintain the strain amplitude and mean stress constant. The strain-controlled data indicate that the application of positive mean stress decreases the fatigue life for a given strain amplitude in air and PWR environments. The data also show that the life reduction is independent of the environments, suggesting that no synergistic effects between the mean stress and the LWR environment occur. The load-controlled experiments confirm that the application of positive mean stress increases fatigue due to cyclic hardening processes. This observation is much less pronounced in the PWR environment. All data were analyzed using the Smith–Watson–Topper (SWT) stress–strain function, which was shown to correlate well with all strain-and load-controlled data with and without mean stress in each environment. In the SWT–life curve representation, the life reduction in the PWR environment was found fully con-sistent with the NUREG-CR6909 predictions.