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Meaning-making is a way of coping when facing adverse events. A paucity of literature suggests other possible factors (e.g. delivery of knowledge) can influence how chronic illness survivors (i.e. stroke survivors in rehabilitation) cope with illness. This article explores the importance and significance of meaning in life as a mediator between perceived stroke knowledge and psychological wellbeing among stroke survivors and how such processes can be applied in practice to promote their psychological wellbeing.A sample of N = 192 elderly aged 60 or above who experienced a recent stroke completed a survey to assess their levels of cognitive ability, physical function, perceived knowledge of stroke, meaning in life, life satisfaction, and depression. Correlation and mediation analyses using the Sobel test were conducted to clarify the role of meaning in life among stroke survivors.Both perceived knowledge of stroke (r = 0.35, P < 0.001) and meaning in life had positive correlations with life satisfaction (r = 0.37, P < 0.001) and a negative correlation with depression. Analyses revealed that meaning in life is a significant mediator between perceived knowledge of stroke and depression (z = −3.71, P < 0.001) and between perceived knowledge of stroke and life satisfaction (z = 3.97, P < 0.001) in two separate models.The role of meaning in life is clear and can affect the dynamics between knowledge of stroke and one’s psychological wellbeing.