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Concerning the importance of psychological well-being (PWB) on physical and mental health, this study aimed at exploring the effective factor on PWB. A multiple mediation analysis was used to investigate whether mindfulness and the presence of meaning in life mediate the predictive relationship between loneliness and PWB. An eligible sample of 412 completed four questionnaires including the De Jong Gierveld Loneliness Scale, the short version of Ryff Scales of PWB, the Mindful Attention Awareness Scale(MAAS), and the Meaning in Life Questionnaire (MLQ). Results demonstrated that loneliness led to a lower level of PWB by reducing mindfulness and the presence of meaning. Results also illustrated that the search for meaning could contribute to the model via contribution to the presence of meaning. It can be asserted that improving mindfulness traits and meaning in life can mitigate the disruptive effect of loneliness on PWB.