ABSTRACT This study aimed to evaluate the effects of partial replacement (750g/kg) of Tifton hay by two cactus cladodes (Nopalea or Opuntia) on the metabolic profile of lambs. Thirty-six uncastrated male Santa Inês lambs (22.0 ± 2.9kg initial body weight) were distributed in a completely randomized design, with three treatments and 12 repetitions. The animals were fed a control diet (Tifton hay as exclusive roughage), Miúda cactus cladodes-based diet or Orelha de Elefante Mexicana (O.E.M.) cactus cladodes-based diet. Blood samples were collected one day before (baseline) and 45 days after the introduction of the tested diets. The Miúda cactus cladodes caused an increase (P=0.055) in the serum activity of the gamma-glutamyl transferase enzyme (53.66U/L) and in the blood content of glucose and fructosamine. The O.E.M. cactus cladodes caused lower (P=0.038) serum cholesterol content (41.33mg/dL). Regardless of the variety, there was a decrease (P=0.001) in the serum content of indirect bilirubin, urea, and sodium, and increase in the serum magnesium concentration. The partial replacement of the Tifton hay by Miúda or O.E.M. cactus cladodes in lamb feeding increases the enzyme activity, indicating liver and/or kidney changes, but does not cause relevant damage to energy, protein, and mineral metabolism.