Abstract Introduction Anorexia nervosa (AN) is a psychiatric illness that results in significant bone loss. Studies examining the neuroendocrine dysregulation that occurs in AN may increase understanding of endocrine systems that regulate bone mass. Peptide YY (PYY) is an anorexigenic peptide derived primarily from the intestine, with actions mediated via activation of Y receptors. We have previously shown that PYY levels are elevated in adolescents with AN. Y2 receptor knockout mice have increased bone mineral density (BMD) and thus PYY may play a role in regulating bone mass. We hypothesized that PYY levels would be inversely associated with BMD in women with AN. Methods This was a cross-sectional study performed in a General Clinical Research Center of 12 adult women with AN, (mean ± SEM) mean age 30.9 ± 1.8 years, BMI 17.1 ± 0.4 kg/m 2, and % ideal body weight 77.5 ± 1.7%. PYY concentrations were measured hourly from 20:00 h to 08:00 h. BMD was measured using dual X-ray absorptiometry (DXA). Results In women with AN, mean overnight PYY levels strongly inversely correlated with BMD at the PA spine ( r = − 0.77, p = 0.003), lateral spine ( r = − 0.82, p = 0.002), total hip ( r = − 0.75, p = 0.005), femoral neck ( r = − 0.72, p = 0.009), total radius ( r = − 0.72, p = 0.009) and 1/3 distal radius ( r = − 0.81, p = 0.002). Body mass index was inversely correlated with PYY level ( r = − 0.64, p = 0.03). Multivariate stepwise regression analysis was performed to determine the contribution of age, duration of AN, BMI, fat-free mass, and PYY to BMD. For PA and lateral spine, PYY was the primary determinant of BMD, accounting for 59% and 67% of the variability, respectively. Fat-free mass and duration of anorexia nervosa were the primary determinants of BMD at other skeletal sites. Conclusions In women with anorexia nervosa, an elevated PYY level is strongly associated with diminished BMD, particularly at the spine. Therefore further investigation of the hypothesis that PYY may contribute to the prevalent bone pathology in this disorder is merited.