Literature indicates that burnout emphasizes its implication in the development of safety issues governing healthcare providers with physical and mental exhaustion associated with it. This study advocated determining burnout and its possible effect on key performance indicators on patient safety outcomes and in the eventual recommendation of preventive actions in policies governing nursing practice. Specifically, it ventured to determine the relationship between nurses’ burnout and their compliance with safety outcomes. A quantitative correlational study was designed to determine 274 purposive samples of registered nurses from participating government and non-government hospitals in Tarlac and Pampanga, Philippines towards their burnout and its relationship on key performance indicators on patient safety outcomes. Data were collected through two standardized self-administered questionnaires, Oldenburg Inventory Scale and the Key Performance Indicators on Patient Safety Outcomes Questionnaire, between February and May 2020. The study revealed that nurses, with a mean age of 27.86 (SD+4.81) years, experienced burnout due to work disengagement (18.10+2.812) and exhaustion (19.81+2.910). Safety guidelines on patient outcomes related to blood management (3.74+0.538) and fall prevention (3.15+0.468) received the highest mean scores with pressure ulcer management (2.82+0.597), the lowest. The study found several significant correlations between nurses’ disengagement, exhaustion, and total burnout with their overall safety culture (r=0.321, p=0.000; r=-0.225, p=0.003). All identified relationships showed a negative correlation suggesting that higher burnout scores are significantly related to lower safety culture scores. Nurses' ability to provide standard-based measures in upholding safety as a priority can be compromised at a considerable level. Recognizing the role of nurses' well-being in healthcare, policymakers should not only emphasize the need for evidence-based, quality, and safe interventions but also investigate the nurses' work conditions and contributory factors for burnout.