The objective of this study was to evaluate the effect of the replacement of different levels of wheat straw with cottonseed plant on performance, digestibility, blood parameters, and rumination behavior of Dalagh ewes. Therefore, 15 ewes with three treatments and five replications were used in a completely randomized design. The treatments consisted of 0, 50, and 100% replacement of wheat straw with cottonseed plant. The whole period of the experiment was carried out in 35 days, consisting of seven days for the adaptation period. Ewe body weight was recorded weekly. Fecal and feed samples were collected on days 31 to 35 for five consecutive days from each treatment to determine digestibility. Blood sampling was done on day 35 and 4 hours after morning feeding. On days 29 and 30, the rumination behavior of ewes was estimated for 24 hours. Results indicated that dry matter intake and weight gain in the second treatment (50% cottonseed plant) increased and feed conversion rate was decreased, but generally performance and digestibility were not affected by treatments. Also, there was no significant difference between experimental treatments in digestibility. Results of the present experiment showed, by increasing the amount of whole cottonseed plant in ewe diets, the concentration of triglyceride increased (p <0.05). The most and the least concentrations of glucose were observed in the first (contained 0% cottonseed plant) and second treatment (contained 50% cottonseed plant), respectively. With the reduction of wheat straw levels in the diet, chewing time and rumination behavior were increased. The difference was not significant in eating, rumination, and chewing behavior. Based on the results of this experiment it could be possible to replace the cottonseed plant in the diet of ewes.