This study investigated physiological and behavioral responses associated with the onset of neonatal calf diarrhea (NCD) in calves experimentally infected with rotavirus and assessed the suitability of these responses as early disease indicators. The suitability of infrared thermography (IRT) as a noninvasive, automated method for early disease detection was also assessed. Forty-three calves either (1) were experimentally infected with rotavirus (n = 20) or (2) acted as uninfected controls (n = 23). Health checks were conducted on a daily basis to identify when calves presented overt clinical signs of disease. In addition, fecal samples were collected to verify NCD as the cause of illness. Feeding behavior was recorded continuously as calves fed from an automated calf feeder, and IRT temperatures were recorded once per day across 5 anatomical locations using a hand-held IRT camera. Lying behavior was recorded continuously using accelerometers. Drinking behavior at the water trough was filmed continuously to determine the number and duration of visits. Respiration rate was recorded once per day by observing flank movements. The effectiveness of inoculating calves with rotavirus was limited because not all calves in the infected group contracted the virus; further, an unexpected outbreak of Salmonella during the trial led to all calves developing NCD, including those in the healthy control group. Therefore, treatment was ignored and instead each calf was analyzed as its own control, with data analyzed with respect to when each calf displayed clinical signs of disease regardless of the causative pathogen. Milk consumption decreased before clinical signs of disease appeared. The IRT temperatures were also found to change before clinical signs of disease appeared, with a decrease in shoulder temperature and an increase in side temperature. There were no changes in respiration rate or lying time before clinical signs of disease appeared. However, the number of lying bouts decreased and lying bout duration increased before and following clinical signs of disease. There was no change in the number of visits to the water trough, but visit duration increased before clinical signs of disease appeared. Results indicate that milk consumption, IRT temperatures of the side and shoulder, number and duration of lying bouts, and duration of time spent at the water trough show potential as suitable early indicators of disease.