CuInSe2 was studied in the as-grown state and after low-temperature (4 K) 2 MeV electron irradiation. The positron bulk lifetime of 235 ps was measured for the unirradiated sample. The positron bulk lifetime was theoretically calculated and is in good agreement with the experimental value. In addition, the defect-related lifetimes for mono-, di-, and trivacancies are theoretically determined. An increased average positron lifetime indicated after electron irradiation the appearance of open-volume defects, most probably of divacancy type. The disappearance of this defect was observed during annealing below 250 K. Other defects were formed leading to a divacancy signal at least stable up to 600 K in the temperature range above 450 K.