The present study was carried out to assess some metabolic indices and nitric oxide in sexually mature, cycling; apparently healthy Sohagi ewes during transition period. At the beginning of the study, 40 ewes were randomly separated into two main groups: pregnant (n = 25) and non pregnant (n = 15) groups. Pregnant group was further subdivided retrospectively into single and twin bearing ewes' subgroups. Blood samples were collected from both main groups. Samples from pregnant ewes were collected at two weeks before and after parturition. Samples were assayed for serum total protein, glucose, urea nitrogen, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and nitric oxide. The results of this study showed no marked change in serum metabolites in single-bearing transition Sohagi ewes except for nitric oxide level. On the other hand, significantly lower (p < 0.05) levels of serum total protein and glucose concentrations were recorded in twin-bearing ewes while liver enzymes and serum urea nitrogen showed significant higher (p < 0.05) compared to control group. Marked improvement in serum metabolites had been recorded after parturition. Only level of nitric oxide production showed significant increase in both single and twin-bearing ewes before parturition compared to control one. While this study indicates the susceptibility of full-term twin-bearing pregnant Sohagi ewes to negative energy balance and oxidative stress before parturition, it showed tolerance of single-bearing pregnant ewes to energy disturbance. Additionally, twin-bearing pregnant Sohagi ewes showed high degree of metabolic adaptation as indicated by remarkable improvement in the blood glucose level shortly after parturition.