Background: Daily hassles (DH) correlate positively with physical and psychological outcomes. Hemispheric lateralization (HL) is the tendency to activate or utilize functions associated with one hemisphere versus parallel regions in the other side. Right-HL is related to longer stress responses and left-HL was found to moderate relationships between DH and mental health. The purpose of this study was to investigate whether coping styles can explain the protective role of Left HL. Methods: In this study, 76 participants completed a daily stressor scale, a physical symptoms scale (PHQ-15), anxiety and depression scales (HADS) and brief scales of coping. HL was measured by the neuropsychological line bisection task, previously validated by electroencephalography. Results: DH was positively correlated with anxiety and physical outcomes in the full sample, and with anxiety only among right-HL people. Furthermore, while in the right HL group, emotion focused coping correlated with both DH and anxiety, in the left HL group, problem focused coping correlated with DH and anxiety. A formal mediation-moderation analysis confirmed this pattern only for denial, which was associated with both DH and anxiety, only in right-HL people Conclusions: The different coping correlates of right and left HL people may be the mechanism which explains the protective role of left HL in the association between DH and mental health. Limitations and additional neurophysiological mechanisms are discussed.