Objective: Lower limb amputation (LLA) leads to several emotional and physical sequelaes that have a negative impact on individuals` life. The objectives of this study were: 1) to analyze the relationship between emotional reactions (anxiety, depression and traumatic stress symptoms) and functionality level, before and after a LLA due to diabetic foot ulcer, and mental/physical quality of life; and 2) to analyze the mediator role of social support between emotional reactions and mental/physical quality of life. Method: A multicenter, longitudinal study with four time assessments: before the surgery, one month, six months, and ten months after surgery, including 206 individuals hospitalized with diabetic foot ulcer indicated for a LLA. The instruments used were the following: Revised Impact of Event Scale; Barthel Index; Hospital Anxiety and Depression Scale and SF-36. Results: Anxiety symptoms before surgery and depression symptoms one month after surgery contribute to Mental Component Score (MCS) ten months after surgery. The level of functionality before and one month after surgery, traumatic stress symptoms one month after surgery as well as satisfaction with social support six months after surgery contribute to the Physical Component Score (PCS), ten months after surgery. Social support was a mediator between traumatic stress symptoms one month after surgery and PCS ten months after surgery. Conclusion: Identifying risk variables and the extent to which and when they affect mental/physical quality of life, will help to develop appropriate psychological interventions to promote quality of life in this population.