A divergent selection experiment for environmental variance of litter size variance was carried out in rabbits over thirteen generations. The aim of this study was to evaluate the inflammatory response in the two lines of the experiment, in order to analyse the effect of selection on susceptibility to diseases after challenging to stressful situations, such as 24 h after the first delivery. A total of 78 females were used in this study, 39 from each line. The line selected for litter size heterogeneity (the high line) showed lower white blood leukocyte count (WBC; −0.87 × 103/µL), lower percentage of basophils (−0.11%), higher concentration of TNF-α (+13.8 pg/mL), and greater concentration of CRP (+38.1 µg/mL) than the line selected for litter size homogeneity (the low line). The high line had also higher concentrations of bilirubin, cholesterol, gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) compared to the low line (difference between lines were +0.08 µmol/L, +0.14 µmol/L, +0.35 U/L and +2.4 U/L, respectively). The high line showed higher inflammatory response than the low line, in accordance with a larger susceptibility to infectious disorders. In conclusion, the line selected to increase litter size environmental variability seems to have poor capacity coping with environmental stressors. Therefore, selection for litter size environmental variability can be a useful way to improve animal welfare.