Background <p>Zinc deficiency is highly prevalent in patients undergoing hemodialysis, and may contribute to cognitive impairment, given its essential role in neurotransmission and neurogenesis. This study aimed to examine the association between serum zinc and cognitive function in this population.</p> Methods <p>This was a cross-sectional study (N = 1207). Cognitive function was assessed by using the Modified Mini-Mental State examination (3MS). The association between serum zinc and 3MS score and its domains were examined by using a linear regression model and ordinal logistic regression model, respectively.</p> Results <p>In total patients, 3MS score and serum zins levels were 91 (82–97) points and 68 (61–76) μg/dL, respectively. Serum zinc level was not associated with 3MS score in adjusted model with 16 potential confounders. However, there was a significant interaction between serum zinc and albumin levels (p = 0.019). Therefore, participants were categorized into 2 subgroups by the median serum albumin level (3.7&#xa0;g/dL) in further analyses. In the lower serum albumin group, the positive association between serum zinc and 3MS was significant after adjustment for 15 potential confounders (p = 0.022). After additional adjustment for both magnesium and phosphate, the association showed a similar positive trend but did not reach statistical significance (p = 0.072). Among the cognitive domains of the 3MS, attention was significantly associated with serum zinc level in participants with lower serum albumin (p = 0.016).</p> Conclusions <p>Lower serum zinc was a novel factor associated with cognitive function, particularly in attention in patients undergoing maintenance hemodialysis with low serum albumin.</p>