The present study investigated the role of fish sludge (FS) as an organic fertilizer in fish ponds alone or in combined with some industrial wastes such as sawdust (SD) and sugar beet pulp (SBP) and their influences on productivity, blood biochemistry, antioxidant and immune status of Nile tilapia compared to the well-known fertilizer cow dung. Fish were distributed into the following experimental groups: control group (with no fertilizers); CD group (cow dung fertilized group); FS group (fish sludge fertilized group); FS + SD (fertilized with fish sludge combined with sawdust); FS + SBP group (fertilized with fish sludge combined with sugar beet pulp) in 3 replicates ponds per each. Fish raised in ponds fertilized with FS + SD, FS, and FS + SBP respectively, recorded higher final weight (FW), weight gain (WG), specific growth rate (SGR), and protein efficiency ratio (PER) values and the lowest feed conversion ratio (FCR) values when compared to the control group. Fish raised in CD fertilized ponds showed significantly higher alanine aminotransferase (ALT) levels. While, FS + SD group had the highest GSH content followed by FS and FS + SBP groups. The catalase (CAT) activity was also significantly higher in FS, FS + SD and FS + SB groups compared to control and CD groups. FS significantly reduced the Malondialdehyde (MDA) content than control and CD groups and a more significant reduction was recorded in FS + SD and FS + SBP groups. The highest total antioxidant activity (TAC) was recorded in the FS + SBP group. The results also showed that FS + SBP followed by FS + SD obtained the highest Alternative Complement pathway (ACH50) activity. FS, FS + SD and FS + SBP groups showed significantly higher lysozyme activity than the CD group. All added fertilizers significantly increased the NBT value compared to the control group. In conclusion, fish sludge showed a more promising property as an organic fertilizer in fish ponds than cow dung, particularly in the presence of adequate water purifying material such as sawdust or sugar beet pulp.