Heat stress may adversely affect physiochemical and immune responses of livestock and alter biological functions. The comfort or thermoneutral zone for livestock, which has long been a subject of research, mainly depends on species, breed, and health. Heat stress is associated with impaired livestock productivity due to reductions in feed intake, growth rates and immunity and changes in blood constituents and biological pathways. In ruminants, elevated temperatures have deleterious consequences on protein synthesis. Exposure of ruminant animals to elevated temperatures may induce release of heat shock proteins (HSPs); HSPs usually enter the blood circulation during tissue damage and causes cell necrosis or death. Additionally, hyperthermia is associated with augmented production of cellular reactive oxygen species (ROS), which cause protein degradation and further decrease protein synthesis by preventing protein translation. Moreover, it has been suggested that high environmental temperatures lead to increased inflammatory signalling in tissues via activation of the nuclear factor kappa B (NF- κB) and tumor necrosis factor alpha (TNF- α) pathways as well as via alteration of skin colour gene (melanocortin 1 receptor (MC1R) and premelanosome protein (PMEL)) expression. Previous proteomics analyses have suggested that heat stress can reduce adenosine triphosphate (ATP) synthesis, alter gluconeogenesis precursor supply, and induce lipid accumulation in the liver with subsequent disturbance of liver structure. This review focuses on the scientific evidence regarding the impact of heat stress on immune and inflammatory responses, antioxidant status, stress biomarkers, skin colour gene (PMEL and MC1R) expression and proteomic profiles in ruminants.