The present study was designed to investigate the effect of using cucumber vines straw (CVS) instead of clover hay in growing NZW rabbit diets without or with prebiotic (mannan oligosaccharide ,MOS) or multi-enzyme (Natuzyme, NZ) supplementation  on nutrient digestibility, nutritive values, caecal microbial activity and itsvolatile fatty acids (VFAs) content, carcass traits and some blood constituents. A total number of 63 six-week old NZW rabbits were randomly divided into 7 groups; each group included 3 replicates of 3 rabbits each and reared in metallic batteries under similar conditions. Graded levels of cucumber vines straw were used to replace  0, 25, 50, 75 and 100%  clover hay, 100%  clover hay level without or with NZ or MOS at 1g/kg diet each, respectively, and  to form 7 pelleted diets similar in all nutrients content and fed to rabbits from 6 to 12 weeks old. Results show that neither dietary CVS till 30% level (100% instead of clover hay) nor supplementation with NZ or MOS had significant effects on caecal VFA content (Acetate,  propionate, Butyrate, Isobutyrate, Valerate, Isovalerate), carcass characteristics (skin+foot, liver, heart, kidneys and abdominal fat weights as percentages of live body weight) and plasma constituents ( total lipids, total cholesterol, creatinine and enzymatic activities of alanine aminotransferase (ALT) and aspertate aminotransferase (AST)). Moreover, all other studied performance traits were not influenced with CVS-diets till 22.5% or 30% level supplemented with NZ or MOS. However feeding 30% CVS-diet without NZ or MOS significantly decreased nutrients digestibility coefficients, nutritive values (digestible crude protein, total digestible nutrients, and digestible energy, caecal pH value, relative carcass yield weights for carcass empty, total edible parts and plasma constituents ( total proteins, albumin and globulin) and increased caecal ammonia (NH₃-N) concentration  compared with those of control. Supplementing NZ or MOS into 30% CVS diet significantly negated (similar to control) all these adverse effects occurred by this level of CVS on studied traits. It could be concluded that CVS can be successfully used till 22.5% level (75% of clover hay) for feeding growing  NZW rabbits without any healthy troubles or adverse effects, such level may be raised till 30% (100% instead of clover hay) in  NZW rabbit diets supplemented with either NZ or MOS.