Abstract Katahdin lambs with decreased post weaning worm egg count estimated breeding values (PWEC EBV) generated greater antibody in response to vaccination and survive better to weaning. Thus, lambs with decreased PWEC values may be more disease resistant and immunocompetent. To test this hypothesis, parasite-resistant St. Croix sheep, (STC, n = 10), and parasite-susceptible Suffolk sheep (SUF, n = 10) were compared with Katahdin sheep divergent in PWEC EBV (HiKAT, n = 10; LoKAT, n = 10) and challenged with lipopolysaccharide (LPS). Sheep were intravenously administered LPS at a dose of 2.5 ug/kg; blood and body temperature data were collected hourly. Behavioral observations were recorded during sampling and videos within pens were obtained 30 min after blood collection. An increase of body temperature by 1 ºC was observed in all groups. Interestingly, STC and SUF temperature peaked at 4 hours whereas LoKAT and HiKAT both peaked at 6 hours. One metric of behavior recorded from video was Sheep Grimace Score (SGS; 1 = normal; 7 = extremely abnormal). Peak SGS in all groups was 3 hours after LPS administration. Main effects of group on SGS indicated a stepwise increase with STC having the least SGS (1.25) and SUF greatest score (2.45) and both groups of Katahdin sheep intermediate (1.65 LoKAT, 2.00 HiKAT; P < 0.001). Evaluation of “return to normal” (RTN), when SGS scores average between 0 and, revealed that STC and LoKAT RTN segregated from the other groups and this occurred at 5.1 and 6.6 hours after LPS treatment, respectively. HiKAT and SUF RTN was at 9.3 and 9.6 hours, respectively. Average SGS RTN in STC and LoKAT were significantly less than HiKAT and SUF (P < 0.01), indicating segregation in behavior. Typical behaviors associated with LPS response, such as fever and ill-behaviors, can be attributed to the rapid and systemic influx of proinflammatory cytokines like tumor necrosis factor alpha (TNFα). Analysis of circulating TNFα revealed similar segregation whereas STC and LoKAT have early TNFα peak at 4 hours and then gradually decline, HiKAT and SUF peak at 9hrs and remain elevated to2hrs. The transition period between these two disparate groups is 6 hours post LPS administration. Thus, TNFα was evaluated before (-2 to 6 hours) and post (7 to 12hours) TNFα shift. With STC sheep having greater TNFα before (45.96 pg/mL, P < 0.001) and SUF sheep having greater TNFα post (47.51 pg/mL, P < 0.001) indicating that despite similar average TNFα there exists timing differences of TNFα that correspond with SGS. These differences are mirrored in the production of TNFα in LoKAT and HiKAT sheep. Taken together these data indicate that early resolvement of TNFα cytokine production within the parasite-resistant groups (STC and LoKAT) is associated with reduced duration of sick behaviors.