A total of 50 California male rabbits at 6 weeks of age were used in this study. They were randomly classified into five groups, 10 rabbits each. The 1^st group, was fed on the basal diet, and considered as the control group, while the other groups [2^nd, 3^rd, 4^th, and 5^th] were the treatment groups, which were fed on the basal diet supplemented with different levels of guava by-product meal (GU) 10,20,30 and 30% +1.0gm/kg/diet of kemzyme respectively as replacement of colver hay, Daily weight gain, feed consumption, and feed conversion ratio were calculated. At the end of experiment (14 weeks), four males from each group were individually weighed and slaughtered.  Plasma samples were collected and stored frozen at-20°C until biochemical analysis for plasma total protein and lipids fractions, plasma minerals (Ca, P, Fe); plasma enzymes (ALT, AST); glucose level, Hemoglobin and hematocrit values as well as thyroid's hormones concentration. Growth performance and carcass traits were also evaluated. Results obtained could be summarized as follow: 1-     Body weight, feed consumption, and feed conversion ratio were not significantly affected by GU supplementation. However, feed conversion was improved in animals that fed guava plus enzyme supplementation, (-4.7: -8.4%). 2-     Liver percentage was significantly affected especially in rabbits that fed on 30% GU plus enzyme (36.6%) than the other groups, but kidney, heart, small and Large intestine, and cecum were  not significantly affected. 3-     Plasma glucose, Ca, phosphorus, total protein and globulin were not significantly affected, however plasma albumin level was increased significantly for rabbits that fed guava and enzyme than control. 4-     Fe level was slightly increased especially in rabbits fed 30% GU than that of the control. 5-     Cholesterol and total lipids were decreased in rabbits that fed on 20 and 30% GU than the other groups. 6-     Thyroid hormones (T₃, T₄)concentrations, N/L ratio, Hemoglobin, and Hematocrit (PVC) were not significantly affected by treatments as compared to the control. 7-     ALT activity was not significantly affected, but AST activity decreased in rabbits that fed 30% GU as compared with the control, (-44.9%). 8-     Total unsaturated fatty acids increased significantly especially in rabbits that fed 20% and 30% plus enzyme than the other groups. 9-     Economical efficiency, performance index as well as production efficiency factor percentages were significantly higher in rabbits fed on GU especially those fed 20 and 30%. From the achieved results the use of guava by-product as a new inexpensive, safe and available natural waste is recommended product to replace the same percentages of clover hay, in rabbit's diets.