Background: Equidae nutritional change increased the frequency of diseases due to inappropriate administration and storage of rations. Although there are reports of ionophore poisoning (IP) and leukoencephalomalacia (LEM) in equidae from Brazil, the concurrent occurrence of both diseases by the same contaminated commercial ration is unprecedented. Therefore, the present paper aims to describe the epidemiological, clinical, laboratorial and pathological findings of concurrent IP and LEM outbreaks in horses.Cases: Eleven farmers from seven different locations in Distrito Federal, Midwestern Brazil, reported sudden clinical signs in 27 horses after the ingestion of commercial pelleted ration. During the farm visits, it was found that the ration brand and batches were identical, and macroscopic evaluation revealed no abnormalities. Eight horses were clinically evaluated and presented hyporexia, apathy, hypermetria, ataxia, dehydration, dyspnea, tongue hypotonia, muscle tremors, tachycardia, facial hypoalgesia, dysphagia, and sporadic or permanent recumbence. Laboratorial changes were restricted to creatine phosphokinase (mean: 1,573.4 ± 16.9 IU/L) and gammaglutamyl transferase (mean: 34.85 ± 29.14 IU/L) serum increases. Pathological evaluation has performed in eight horses presenting pallor and whitish striations in the gluteal, longissimus dorsi, femoral quadriceps muscles and myocardium, varying from mild to moderate. One horse also showed a soft and yellowish focal area on the right temporal lobe white matter. Microscopically, alterations in skeletal and cardiac muscle tissues included striated muscle fibers and cardiomyocytes segmental necrosis, characterized by sarcoplasmic fragmentation with clusters of eosinophilic debris, cellular retraction and hypereosinophilia. Histological alterations in the central nervous system of one horse were characteristic of LEM. Ration samples analysis revealed the presence of salinomycin (2,384.91 ± 100.7 ppm), narasin (144.15 ± 7.75 ppm) and fumonisins (0.87 to 4.09 ppm). Eight hospitalized horses were submitted to clinical therapy (gastric lavage and application of activated charcoal; fluid-electrolyte imbalance correction, intravenous dimethylsulfoxide, tocopherol and selenium supplementation). Four (50%) horses had permanent sequelae (muscle weakness and mild ataxia), two (25%) recovered without sequelae, and two (25%) were euthanized due to inability to stand and poor prognosis. Considering the total number of affected horses, mortality rate reached 59.25% (16/27).Discussion: Usually ionophores are safely used in livestock and bird production at the recommended doses. However, horses are among the most susceptible species and do not tolerate any exposure to the substance. The outbreaks herein occurred due accidental ionophore contamination of commercial ration at the industry probably by manufacturing process technical failures. Similarly, fumonisins contamination may be caused by feedstock inadequate storage at the industry, or improper ration storage in the farms. The suspicion of two concurrent diseases (IP and LEM) in the horses of these outbreaks was confirmed through the association of epidemiology, clinical signs, pathological findings and measurement of ionophores and fumonisins in the commercial ration. We reiterate the difficulty in diagnosing associated clinical syndromes, especially when high-lethality diseases are involved.