Background <p>There is evidence that caring for children with chronic diseases has an impact on the mothers' quality of life in various settings, but minimal evidence exists regarding this influence in Oman.</p> Objective <p>To assess the factors associated with the quality of life (QoL) among Omani mothers caring for children with chronic diseases.</p> Methods <p>A cross-sectional descriptive design was utilized. The World Health Organization Quality of Life questionnaire and the Zarit Burden Scale were used to evaluate study variables.</p> Results <p>The mean score for domains of QoL of physical health, psychological health, social health, environmental health, and general quality of life, were 42.36, 48.66, 45.18, 39.88, 62.90, respectively. The main factors associated with the QoL were perceived caregiving burden, mother age, and family income.</p> Conclusion <p>Tailored support services are needed to enhance care for mothers to promote their quality of life while fulfilling caregiving responsibilities.</p>