Background <p>Family caregivers of individuals with disabilities often experience a significant caregiver burden, which has been associated with higher levels of depressive symptomatology. However, limited research has examined the role of moderating variables such as unwanted loneliness and meaning in life in this context. This study aims to analyze the presence of depressive symptoms among female informal caregivers and the modulating factors involved, highlighting meaning in life as a key psychological variable in the caregiving process.</p> Methods <p>The sample consisted of 104 informal caregivers of individuals with disabilities, all of whom were women. Individual interviews were conducted, during which participants completed an assessment protocol comprising a sociodemographic questionnaire and the following standardized instruments: the Zarit Caregiver Burden Interview, the UCLA Loneliness Scale, the Patient Health Questionnaire-9 (PHQ-9), and the Purpose in Life Scale (PIL-10).</p> Results <p>Findings revealed that meaning in life partially mediates the relationship between caregiver burden, unwanted loneliness, and depressive symptoms, acting as a protective factor against emotional distress in informal caregivers.</p> Conclusions <p>Our results suggest that meaning in life is a key mediating variable in the link between caregiver burden, loneliness, and depression. We conclude that meaning in life is a relevant construct for understanding caregiver stress and should be considered in therapeutic interventions aimed at supporting informal caregivers.</p>