This study aimed to describe metabolic, oxidative, and mineral blood profiles of Saanen does through lactation compared with Mediterranean breed clusters (Maltese and Rossa Mediterranea, and Jonica, Garganica, and Girgentana). Milk and blood samples of 57 dairy goats (9–10 goats per breed) were collected from the 2nd to the 30th week of lactation every 2–3 weeks. Saanen showed greater milk yield and somatic cell score, and lower fat and protein percentage through lactation (p < 0.05) than the Mediterranean breed clusters. Blood analysis revealed that stage of lactation had a greater impact than breed cluster, except for uric acid, alkaline phosphatase, and aspartate aminotransferase. Plasmatic non-esterified fatty acids indicated a greater negative energy balance in Saanen than the other breed clusters during early and medium lactation stages (p < 0.05). Serum Cl, Mg, and Ca increased in all the breed clusters from early to the following stages of lactation (p < 0.05). No significant prooxidant/antioxidant imbalances were detected in any of the three clusters during the entire lactation. In conclusion, Mediterranean breeds tended to recover earlier from negative energy balance than Saanen, but effects of breed or stage of lactation on long-term oxidative stress indicators were not evident.