The evidence regarding the association between mood and cognitive function is conflicting, suggesting the involvement of moderating factors. This systematic review aimed to assess whether cognitive reserve moderates the association between mood and cognition in older people. Cognitive reserve was considered in terms of the three key proxy measures – educational level, occupation, and engagement in cognitively stimulating leisure activities – individually and in combination. Sixteen studies representing 37,101 participants were included in the review. Of these, 13 used a measure of education, one used a measure of occupation, two used a measure of participation in cognitively stimulating activities, and one used a combination of these. In general, cognitive reserve moderated the association between mood and cognition, with a larger negative association between mood and cognition in those with low cognitive reserve than in those with high cognitive reserve. Further research utilizing multiple proxy measures of cognitive reserve is required to elucidate the associations.