Calf diarrhea is a major cause of economic loss in the cattle industry. Identifying biomarkers associated with the pathological conditions may provide beneficial guidelines for detecting disease progression and monitoring effectiveness of therapeutic agents in calves suffering from diarrhea. The objective of this research was to find out biological factors associated with calf diarrhea, based on clinical findings and the presence of enteric pathogens. Fecal and blood samples were obtained from 73 non-diarrheal and 42 diarrheal calves. The presence of enteric pathogens, hemato-chemical parameters, acute phase proteins, and pro-inflammatory cytokines were investigated in the samples. According to the presence of diarrhea and pathogens, the calves were classified into healthy (n=35), subclinical (non-diarrheal but pathogen-positive, n=36), infectious diarrheal (diarrheal and pathogen-positive, n=39), and unknown diarrheal groups (diarrheal but pathogen-negative, n=3). The presence of bovine coronavirus, bovine rotavirus group A, and Cryptosporidium spp. were significantly associated with the development of calf diarrhea (P<0.05). The infectious diarrheal group showed increases in monocyte percentages and blood urea nitrogen level and the decreases in glucose, potassium, and phosphorus levels (P<0.05). Moreover, inflammatory proteins such as haptoglobin, fibrinogen, interleukin-6, and tumor necrosis factor-alpha were elevated in the infectious diarrheal group compared to the healthy group (P<0.05). The current study identified altered blood biological factors in calves with infectious diarrhea. The results suggested that these factors may be useful targets for monitoring animal health in calf diarrheal disease, especially infectious diarrhea.