This paper reports on the fatigue performance of an ultrafine-grained (UFG) interstitialfree (IF) steel deformed at various mean stress levels. The UFG microstructure was achieved using equal channel angular extrusion processing at room temperature (RT) and along an “efficient” route, giving way to the formation of high angle grain boundaries (HAGBs) with a high volume fraction. The current study not only confirms the previous finding that a high volume fraction of HAGBs promotes cyclic stability, but also inquires into the role of mean stress level on the cyclic stability. It is shown that the UFG IF steel exhibits a stable cyclic deformation response in the lowcycle fatigue regime within the medium applied mean stress range of -75 to 75 MPa. The corresponding fatigue lives can still be predicted with the Smith-Watson-Topper approach within this range. Furthermore, the present study demonstrates that the evolution of mean strains with cyclic deformation can be linked to the evolution of mean stresses in strain-controlled loading.