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 3 Si 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 2 BeF 4 ), natural lithium and eutectic lithium (Li 17 Pb 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 2 BeF 4 ) coolant blankets, followed by Eutectic lithium (Li 17 Pb 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 2 BeF 4 coolant that volume fraction is 62.5% after 48 months. The lowest CFFE value (3.80%) is in U 3 Si 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 3 Si 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 3 Si 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 3 Si 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 240 Pu 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 240 Pu 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.