High-entropy alloys (HEAs) have prospects for use as nuclear structural materials. Helium irradiation can form bubbles deteriorating the structure of structural materials. The structure and composition of NiCoFeCr and NiCoFeCrMn HEAs formed by arc melting and irradiated with low-energy 40 keV He2+ ions and a fluence of 2 × 1017 cm−2 have been studied. Helium irradiation of two HEAs does not change the elemental and phase composition, and does not erode the surface. Irradiation of NiCoFeCr and NiCoFeCrMn with a fluence of 5 × 1016 cm−2 forms compressive stresses (−90 … −160 MPa) and the stresses grow over −650 MPa as fluence increases to 2 × 1017 cm−2. Compressive microstresses grow up to 2.7 GPa at a fluence of 5 × 1016 cm−2, and up to 6.8 GPa at 2 × 1017 cm−2. The dislocation density rises by a factor of 5–12 for a fluence of 5 × 1016 cm−2, and by 30–60 for a fluence of 2 × 1017 cm−2. Stresses and dislocation density in the HEAs change the most in the region of the maximal damage dose. NiCoFeCrMn has higher macro- and microstresses, dislocation density, and a larger increase in their values, with an increasing helium ion fluence compared to NiCoFeCr. NiCoFeCrMn a showed higher radiation resistance compared to NiCoFeCr.