Abstract Background The importance of cerebrospinal fluid (CSF) diagnostics for psychiatry is growing. The CSF/blood albumin quotient (Q_Alb) is considered to be a measure of the blood–CSF barrier function. Recently, systematically higher Q_Alb in males than in females was described in neurological patients. The aim of this study was to investigate whether a sex difference could also be detected in a well-characterized psychiatric cohort. Methods The patient cohort comprised 989 patients, including 545 females and 444 males with schizophreniform and affective syndromes who underwent CSF diagnostics, including Q_Alb measurement. The basic CSF findings and antineuronal autoantibody data of this cohort have already been published. This re-analysis employed analysis of covariance with age correction for Q_Alb mean values and chi²-testing for the number of increased age-corrected Q_Alb levels to investigate sex differences in Q_Alb. Results The Q_Alb levels were elevated above reference levels by 18% across all patients, and a comparison between male and female patients revealed a statistically significant sex difference, with increased values in 26% of male patients and a corresponding rate of only 10% in female patients (chi² = 42.625, p < 0.001). The mean Q_Alb values were also significantly higher in males (6.52 ± 3.69 × 10^–3) than in females (5.23 ± 2.56 × 10^–3; F = 52.837, p < 0.001). Discussion The main finding of this study was a significantly higher Q_Alb level in male compared to female patients with psychiatric disorders, complementing previously described sex differences in neurological patient cohorts. This result indicates bias from some general factors associated with sex and could be partly explained by sex differences in body height, which is associated with spine length and thus a longer distance for CSF flow within the subarachnoid space down the spine from the occipital area to the lumbar puncture site in males compared to females. Hormonal influences caused by different estrogen levels and other sex-specific factors could also play a relevant role. The significance of the study is limited by its retrospective design, absence of a healthy control group, and unavailability of exact measures of spine length.