Original Scientific Article Septicemia is a significant threat to newborn calves, often due to inadequate colostrum intake in the first day of life. The study aimed to assess the effects of a newly developed herbal formulation on septicemia induced by Escherichia coli strain O111:H8. Ten Holstein-Friesian calves aged 8-10 days were divided into two groups. Experimental septicemia was induced for all calves (n=10). The treatment group (n=5) received a herbal formulation containing extracts from Rosa canina, Urtica dioica, Tanacetum vulgare, selenium, flavonoids, and carotenes, in addition to antibiotics. The control group (n=5) received a placebo (5% dextrose) along with antibiotics for five days. The animals were monitored for 14 days. Blood samples were analyzed for cytokines, cardiac enzymes, renal function, and total antioxidant capacity before and after treatment. The treatment group had non-significantly higher CD4+ counts compared to the control. The serum level of IL-6 increased after treatment, with a considerable difference between the groups at 72 h (p=0.0014). The herbal formulation positively impacted renal and cardiac function evidenced by decreased cardiac troponin I levels and increased total antioxidant capacity (TAC). Lactate dehydrogenase (LDH) levels changed significantly over time (p<0.05), with a positive correlation between ECG changes and peak LDH levels (p<0.05). The increased cytokines beside ameliorative effects on heart and kidney functions suggest that the herbal drug may possess immunomodulatory and anti-inflammatory properties that aid in managing the inflammatory response during sepsis. These findings support the use of this herbal-based drug as an adjunctive treatment in veterinary practices for managing septicemia in calves. https://macvetrev.mk/LoadArticlePdf/361 2025-03-15 87 99 https://doi.org/10.2478/macvetrev-2025-0018 calves septicemia Rosa canina Urtica dioica Tanacetum vulgare Masoomeh Heidari Sureshjani false 1 Department of Public Health and Food Safety, General Direction of Veterinary Organization, Chaharmahal and Bakhtiari Province, Iran AUTHOR Marzieh Mokhber Dezfouli false 2 Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Science, 1995614331 Tehran, Iran AUTHOR Zohre Eftekhari z_eftekhari@pasteur.ac.ir false 3 Biotechnology Department, Pasteur Institute of Iran, 3159915111 Tehran, Iran LEAD_AUTHOR Samad Lotfollahzadeh false 4 Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran AUTHOR Hesam-aldin Akbarein false 5 Department of Food Hygiene and Control, Faculty of Veterinary Medicine, University of Tehran, 14199631113 Tehran, Iran AUTHOR Mokhber Dezfouli, M.R., Mohammadi, H.R., Nadalian, M.G., Nazem Bokaee, Z., Hadjiakhoondi, A., Nikbakht Borujeni, G.R., et al. 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