The possibility of nuclear fuel rejuvenation in fusion reactors is investigated for different fuels and coolants. Neutronic performances of the deuterium–tritium (D–T) driven hybrid blankets, fuelled with UN, UC, UO 2 and U 3Si 2, in four different cases, are investigated under first wall load of the 5 MW/m 2. The fissile fuel zone considered to be cooled with four coolants: air, flibe (Li 2BeF 4), natural lithium and eutectic lithium (Li 17Pb 83) with volume fraction ratio of 29.5, 45.5 and 62.56%. The behaviour of the fuels mentioned above are observed during 48 months for discrete time intervals of Δt =15 days and by a plant factor (PF) of 75%. At the end of the operation time, calculations have shown that cumulative fissile fuel enrichment (CFFE) values have varied between 3.80 and 8.1% depending on the fuel, volume fraction and coolant type. The best enrichment performance is obtained in flibe (Li 2BeF 4) coolant blankets, followed by Eutectic lithium (Li 17Pb 83), air whereas natural lithium coolant shows a poor rejuvenation performance in all fuels. CFFE reach maximum value (8.1%) in UO 2 fuelled blanket (in Row #1) and Li 2BeF 4 coolant that volume fraction is 62.5% after 48 months. The lowest CFFE value (3.80%) is in U 3Si 2 fuelled blanket (in Rows #6 and 7) and natural lithium coolant that volume fraction is 62.56% at the end of the operation period.The enrichment would be sufficient for LWR reactor. The best tritium breeding ratio (TBR) is obtained in U 3Si 2 fuelled blanket with natural lithium coolant, and followed by UC, UO 2, UN with the same coolant. At the beginning of the operation, TBR values were 1.459, 1.502 and 1.554 in U 3Si 2 fuelled blanket with natural lithium coolant 1.414, 1.474 and 1.547 in UC fuelled blanket with natural lithium coolant for volume fraction of 29.5, 45.5 and 62.56%, respectively. At the end of the operation, TBR reach 1.511, 1.559 and 1.613 in U 3Si 2 fuelled blanket and 1.467, 1.532 and 1.609 in UC fuelled blanket for volume fraction of 29.5, 45.5 and 62.56%, respectively. TBR values are higher than unity. Therefore, investigated hybrid blanket is self-sufficient for all fuel mixture and coolants. The isotopic percentage of 240Pu is higher than 5% in all modes with flibe coolant, so that the plutonium component in these modes can never reach a nuclear weapon grade quality during the operation period. This is a very important safety factor. The isotopic percentage of 240Pu is lower than 5% in all blanket with air, natural lithium, and eutectic lithium coolant. In these modes, operation period must be increased for safety.