This study was developed to evaluate the clinical, hematological, and performance parameters of calves affected by diarrhea caused by the bacterial enteric pathogen Escherichia coli, treated with three different protocols containing sulfonamides. Fourteen Holstein calves were monitored from birth to 60 days of age, and divided into 3 groups. Group 1 (n=5) animals were treated with 80 g of Kaopek®, Ibasa, Brazil, administered orally (BM), dissolved in 160 ml of water every 24 h; Group 2 (n=4) received IM sulfadiazine and trimethoprim (Ibatrim®, Ibasa, Brazil), and Group 3 (n=5) animals were treated with 80 g of Kaopek®, Ibasa, Brazil, which is made up of 16 g of phthalylsulfathiazole, associated with 2.28 g neomycin sulfate, 1.6 g of pectin, and 80 g of kaolin, dissolved in 160 ml of water and administered every 24 h by mouth, in addition to sulfadiazine and trimethoprim (Ibatrim®, Ibasa, Brazil), at a daily dose of 16 mg/kg live weight, through IM injection. During the study, the animals were clinically evaluated, and once they were diagnosed with diarrhea, feces samples were collected to identify the bacterial enteric pathogen, antibiogram, polymerase chain reaction (PCR), and coproparasitological exams. Blood samples were collected to evaluate the hematological profile, and the performance profile was monitored weekly. In the clinical examination, all calves presented a reduction in body temperature (<39.2°C) and some improvement in hydration after treatment (p=0,31). However, group 2 had a better concentration of lymphocytes and TP concerning the other animals, as well as better performance. Besides, E.coli was detected in 100% of feces samples. Thus, the therapeutic protocols with sulfonamides used to treat bovine neonatal diarrhea were effective in the clinical improvement of the animals. Nonetheless, the protocol with systemic therapy using sulfadiazine and trimethoprim (Ibatrim®, Ibasa, Brazil) intramuscularly, provided better performance, with better weight gain, and body development of the animals.(AU)