Background: Cystic fibrosis bone disease (CFBD) is a common comorbidity in adult people with cystic fibrosis (pwCF), resulting in an increased risk of bone fractures. This study evaluated the capacity of artificial intelligence (AI)-assisted low-dose chest CT (LDCT) opportunistic screening for detecting low bone mineral density (BMD) in adult pwCF. Methods: In this retrospective single-center study, 65 adult pwCF (mean age 30.1 ± 7.5 years) underwent dual-energy X-ray absorptiometry (DXA) of the lumbar vertebrae L1 to L4 to determine BMD and corresponding z-scores and completed LDCTs of the chest within three months as part of routine clinical care. A fully automated CT-based AI algorithm measured the attenuation values (Hounsfield units [HU]) of the thoracic vertebrae Th9–Th12 and first lumbar vertebra L1. The ability of the algorithm to diagnose CFBD was assessed using receiver operating characteristic (ROC) curves. Results: HU values of Th9 to L1 and DXA-derived BMD and the corresponding z-scores of L1 to L4 showed a strong correlation (all p < 0.05). The area under the curve (AUC) for diagnosing low BMD was highest for L1 (0.796; p = 0.001) and Th11 (0.835; p < 0.001), resulting in a specificity of 84.9% at a sensitivity level of 75%. The HU threshold values for distinguishing normal from low BMD were <197 (L1) and <212 (Th11), respectively. Conclusions: Routine LDCT of the chest with the fully automated AI-guided determination of thoracic and lumbar vertebral attenuation values is a valuable tool for predicting low BMD in adult pwCF, with the best results for Th11 and L1. However, further studies are required to define clear threshold values.