Objectives: To investigate changes of cognitive performances in female elderly patients with osteoporosis and to determine whether any impairments can be attributed to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Methods: This cross-sectional study included 277 postmenopausal women, who were divided into an osteoporosis patients group (n = 170) and an age, gender and educational history matching control group (n = 107). All the subjects completed a set of neuropsychological tests for the elderly for cognitive assessment, which included measures of executive function, episodic memory, attention and processing speed, semantic memory, and visuospatial construction. Blood biomarkers for osteoporosis, as well as diurnal rhythms of cortisol levels were used as cognitive performance correlation parameters in linear multivariate regression analyses. Results: Individuals with osteoporosis had poorer cognitive scores (P < 0.001). When dividing the osteoporosis patients according to their Mini-Mental State Examination scores into mild cognitive impairment (MCI) and normal cognitive (NC) performance groups, Auditory Verbal Learning trial 1-5 scores were lower (P = 0.006) and Trail Making Test-A scores were higher (P = 0.05) in the MCI compared to the NC group. Further comparison of the MCI and NC groups revealed that declarative memory was inversely associated with cortisol levels (P < 0.001), but this association became marginal when 25-hydroxy vitamin D was included in the linear multivariate regression analyses (P = 0.06). Conclusions: Patients with osteoporosis are prone to cognitive impairments especially declarative memory deficits. The cognitive impairment may be the result of HPA axis dysregulation but 25-hydroxy vitamin D serum concentrations might be compensatory or even a potent contributing factor.