Despite many advances in management and housing of dairy calves, 1 in 10 US dairy heifers die before weaning. A better understanding of the internal and external stimuli that contribute to the calf’s physiological and behavioral responses to stressors is needed to reduce the risk of morbidity and mortality. Feeding calves their first meal is crucial, as successful passive transfer reduces mortality by 60%. There appears to be sexually dimorphic immune and stress responses in young cattle, but more research is needed to determine if this is caused by human-bias for female calves. After that first feeding, 1 in 10 heifers and most bull-calves in the US are transported to specialized calf-raising facilities, yet there is a lack of information of the newborn calf stress response during transit and handling. Whether calves are raised off-site or at a calf-ranch, individual housing systems are commonly used in the US to reduce the risk of pathogen exposure and provide individual feeding and healthcare. However, there may be health, growth, and social benefits for calves in alternative systems that have increased space-allowance or group housing. Disbudding and castration are typically performed at an early age for dairy calves, during the pre-wean stage. These stressors often take place when the calf has decreased passive-transfer Ig and immunity is developing. There is limited availability of pain-mitigation through anesthetics and analgesics, but there is evidence that analgesics attenuate supressed leukocyte function during these procedures. Milk replacer (MR) and milk quality may alter immunity. Solid-feed intake is a primary measure for determining “weaning-readiness,” but some MR formulas may influence the calf’s oral behaviors before weaning, therefore alternate weaning-methods may need to coincide with alternate MR formulas. The calf’s behavioral and stress response at weaning may influence its immunity during the transition from individual to group housing (commingling). Alternate commingling strategies and nutritional supplements may help with this transition, but more research is needed to explore feasible alternatives. Optimizing the calf’s health and well-being at these early-stages may improve its long-term health and behavioral strategies.