Abstract: Background and Objective: High ambient temperature can cause heat stress and evokes a combination of change in blood biochemicals and reproduction of rabbit. This study targeted to investigate the effect of Spirulina platensis, vitamin E and their combination on in vivo and in vitro reproductive performance and some physiological and health indicators of heat stressed rabbit does. Materials and Methods: Nili-parous rabbit does (n = 80) were allocated to 4 groups. Does in the 1st group were fed commercial complete feed diet, while those in the 2nd, 3rd and 4th were fed complete feed diet with Spirulina platensis (300 mg kg–1), vitamin E (100 mg kg–1 diet) and Spirulina platensis+vitamin E kg–1 diet, respectively. All does were naturally mated with fertile bucks (5 bucks/group). Results: The does in the 2nd group showed significantly (p<0.05) better reproductive performance (conception rate, kindling rate and litter size), lipid profile (total lipids, cholesterol, triglycerides, high and low density lipoproteins, antioxidant capacity (total antioxidant capacity, glutathione, malondialdehyde, glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase), immunity (lysozyme, IgG and IgM), ovulatory response (corpora lutea number and ovulation rate), embryo quality and hatched blastocysts production with higher cell number and inner cell mass as compared to other groups. Conclusion: Dietary supplementation with Spirulina platensis (300 mg kg–1 diet), in comparing with vitamin E (100 mg kg–1 diet) or their combination at the same levels, had positive impact on reproductive performance of rabbit does used in breeding program under heat stress condition in Egypt.