Objective People with brain tumour experience complex and distressing symptoms. Neuropsychological impairment is proposed to have a negative impact on subjective well-being; however, research is yet to examine the influence of estimated premorbid IQ on this relationship. This preliminary study investigated the moderating effect of estimated premorbid IQ on the relationship between global neuropsychological status (GNF) and depression and quality of life. Methods 73 adults (51% male) aged 21–65years with primary brain tumour (52% benign) were administered a test battery assessing estimated premorbid IQ, GNF, depression (Depression Anxiety Stress Scales) and quality of life (Functional Assessment of Cancer Therapy, FACT). Results A series of two-way analysis of covariance (ANCOVA) controlling for education found a significant interaction between estimated premorbid IQ (low average to average vs high average) and GNF (low vs high) on levels of depression (p <.05) and FACT emotional well-being (p <.05). For these outcomes, individuals with high average estimated premorbid IQ and low GNF reported better well-being than those with low-average to average estimated premorbid IQ and low GNF. Higher GNF was related to greater functional well-being (p <.01) irrespective of estimated premorbid IQ. Conclusion The finding that higher premorbid cognitive ability buffers the effect of neuropsychological impairment on emotional well-being after brain tumour advances understanding of the role of cognitive reserve in adjustment to neurological disorders.