Stress in caregivers of the elderly occurs due to a combination of tasks during caring for the elderly. Several factors affect stress levels, namely the regulation of emotions and spirituality. This study aims to determine the relationship between stress with emotional regulation and spirituality in caregivers of the elderly at Karangmojo 1 Health Center, Gunungkidul. The research subjects were caregivers of elderly, numbering 36 people, obtained by purposive sampling. Data takes using an emotional regulation scale (Alpha Cronbach's reliability coefficient of 0.871), spirituality scale (Alpha Cronbach's reliability coefficient of 0.921), and stress in caregivers of elderly range (Alpha Cronbach's reliability coefficient of 0.905). The results showed that r = 0.485 and Sig. 0.012 (p <0.05), so there is a correlation between stress and emotional regulation and spirituality. The higher the control of emotion and spiritual level, the lower the pressure that occurs. This research expects to provide input in the realm of psychology; for example, it can be used as a reference and help caregivers deal with stress by increasing their emotional and spiritual regulation skills.