Disease is a leading cause of diminished welfare and productivity in pig systems, but its spread among pigs within commercial herds can be limited through early detection. Identifying specific behavioral changes at the onset of disease can have a substantial diagnostic value by improving treatment success through timely intervention. Our study aimed to identify key behaviors that visibly change at the group level when only a few individuals are acutely sick. First, we quantified the behavioral changes seen during an acute health challenge in groups of pigs, using total pen vaccination as an artificial sickness model. Then we investigated the minimum proportion of sick pigs needed to detect group level behavioral changes using three treatments: a control (Con; 0% pigs), low (±20% pigs), or a high (±50% pigs) number of pigs vaccinated in the pens. Total pen vaccination in Trial 1 produced group level behavioral changes, including reduced feeding (P < 0.001), non-nutritive visits to the feeder (P < 0.01), drinking (P < 0.001), standing (P < 0.001), and interaction with pen enrichment (P < 0.001), accompanied by increased lying rates (P < 0.01) and elevated body temperatures (P < 0.001), confirming that vaccination is an appropriate model to study effects of acute sickness. In Trial 2, group level declines in interaction with the enrichment device (P < 0.001) and standing rates (P = 0.064), along with an increase in pen lying rates (P < 0.001), were apparent in the Low treatment when compared to the Con rates, which suggests these key behaviors could serve an important diagnostic value for early disease detection in groups. These changes lasted for up to 3 h post vaccination. In contrast, feeding rates (treatment × time of day: P < 0.01) only showed a decrease from the Con in the High treatment after vaccination, with pen drinking showing a similar trend (treatment: P = 0.07), suggesting that these behaviors would be more appropriate for confirming the spread of disease within a herd. Identifying key behaviors that alert to the presence of disease is critical to further refine automated early warning systems using pen level sensors for commercial pig operations.