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The present study was conducted to assess the comparative physiological responses of stress in sheep selected for resistance or susceptibility to Haemonchus contortus in the semi-arid region during different seasons. A total of 20 adult Malpura sheep from resistant and susceptibility line were selected for study. The intensity of strongyle infection, blood biochemical and cortisol levels were estimated monthly basis while meteorological data were collected everyday throughout the year. The temperature-humidity index was the highest during dry-hot season. The faecal egg count increased significantly (p < 0.05) during June-August (rainfall season) in susceptible sheep as compared to resistant sheep. The plasma cortisol level increased significantly (p < 0.05) in both the groups during dry hot (March-May) season and it remained higher in the susceptible line till June-August. The total plasma protein reduced significantly during hot-humid with scantly rainfall (September-November) season as compared to other season in susceptible line. It is pertinent to conclude that though sheep remained in stress during dry hot (March-May) season, but effects of stress on the intensity of strongyle infection and blood biochemical were better tolerated by animals of resistant line during hot-humid season compared to susceptible line under semi-arid region.