As the incidence of cystic fibrosis (CF) bone disease is increasing, we analyzed cystic fibrosis transmembrane conductance regulator (CFTR) deficient mice (CF mice) to gain pathogenic insights. In these studies comparing adult (14 wk) CF and C57BL/6J mice, both bone length and total area were decreased in CF mice. Metaphyseal trabecular & cortical density were also decreased, as well as diaphyseal cortical & total density. Trabecular bone volume was diminished in CF mice. Female CF mice revealed decreased trabecular width and number compared to C57BL/6J, whereas males demonstrated no difference in trabecular number. Female CF mice had reduced mineralizing surface and bone formation rates. Conversely, male CF mice had increased mineralizing surface, mineral apposition and bone formation rates compared to C57BL/6J males. Bone formation rate was greater in males compared to female CF mice. Smaller bones with decreased density in CF, despite absent differences in osteoblast and osteoclast surfaces, suggest CFTR influences bone cell activity rather than number. Differences in bone formation rate in CF mice are suggestive of inadequate bone formation in females, but increased bone formation in males. This pro-anabolic observation in male CF mice is consistent with other clinical sex differences in CF.