Aflatoxicosis is a serious health condition resulted from aflatoxin (AF)-producing fungi. Major health threats resulted from AFs and reflect on the livestock industry with great economic losses. There are limited scientific evidences concerning the AFs in ruminant, therefore it is important to evaluate AFs health hazards in cattle. Here, we investigate biochemical, oxidative stress, and postmortem changes associated with unexpected acute bovine aflatoxicosis. Seventy-two cattle were suffered from aflatoxisocis. Depression and inappetence were predominant clinical findings of the diseased animals. Analysis of feedstuffs revealed presence of aflatoxin B1 (AFB1). The AF-intoxicated animals showed a significant increase in alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), serum creatinine (SCr), catalase (CAT), and malondialdehyde (MDA) levels. Moreover, a significant decrease in total protein (TP), magnesium (Mg), and reduced glutathione (GSH) were also seen. Hepatomegaly, enlarged gallbladder as well as congestion of the intestine and kidney were observed. This study elucidates the critical and constructive measurements needed for the prevention of the AFs hazardous effects to livestock for the future control of AF outbreaks. Conducting series of diagnostic assays reflect the marked health condition alterations in the biochemical and antioxidant status of the AF-intoxicated cattle.