Environmental effects on pathogen abundance and access are precursors to mastitis. Indeed, high heat and humidity, and unsanitary housing and equipment, are associated with greater pathogen load and exposure. Although less is known about effects of environment on a cow's ability to resist infection, several indicators suggest that it can affect pathogen responses. Mastitis incidence and bulk tank somatic cell count vary with season, typically peaking in summer. Recent controlled studies have revealed that heat stress exposure results in changes in the microbiome of the cow and her environment, which may relate to negative effects on milk quality and cow health. Alternatively, specific pathogen loads may vary based on housing dynamics rather than associations with physical environment. Indeed, housing-related stressors, such as overcrowding and social group challenge, influence secretion of glucocorticoids, thus affecting pathogen resistance in the cow. Two key seasonal variables are photoperiod and temperature, specifically the heat stress consequent to elevated temperature and humidity. Shifts in light duration regulate immune function in other species, but apparently have limited effect on udder health of lactating cows. In contrast, in dry cows, short days increase peripheral blood mononuclear cell number and are associated with lower somatic cell count in the next lactation, compared with long days. With heat stress, elevated body temperature directly affects expression of immune-related genes in mammary tissue. Responses depend on duration of exposure and feature acute upregulation of immune-signaling pathways, followed by enrichment of other immune-related pathways after prolonged exposure. Most responses are transient and recover within 1 wk. Functionally, heat stress impairs some aspects of acquired immunity in dry cows, including antigen responses and lymphocyte proliferation, but apparently not innate immune function. However, heat stress in late gestation reduces neutrophil phagocytosis and killing in vitro, and neutrophils in circulation are reduced in vivo as are responses to pathogen challenge in the subsequent lactation. A holistic understanding of the complex interplay of environment, pathogens, and host is needed to inform advances in this area.