We investigated whether computed tomography (CT) Hounsfield unit (HU) values of the S1 screw trajectory can predict screw loosening after lumbosacral fixation. We analysed 102 patients (58 men and 44 women) who underwent L5-S1 interbody fusion between April 2018 and October 2019. We reviewed the characteristics of patients including body mass index, smoking, comorbidity with diabetes mellitus, and interbody fusion types. Bone mineral density (BMD) was obtained from the lumbar spine and total hip using dual-energy X-ray absorptiometry. Additionally, we reviewed the S1 screw lengths and diameters. HU values of both L1 vertebral bodies and bilateral S1 screw trajectories were measured on preoperative CT. At six months postoperatively, S1 screws on CT were assessed. Screws with a 1 mm or more radiolucent zone were defined as “loosening”. Seventeen patients had loosened screws, and 85 patients did not. The patient characteristics did not significantly differ between the two groups. Both total hip BMD and L1 HU values were low in the loosening patient group (both p = 0.03). Of the 204 total S1 screws, 25 screws were loosened, and 179 screws were not. The screw length was short (p = 0.01), and the HU value of the S1 screw trajectory was low (p < 0.001) in the loosening screw group. Based on receiver operating characteristic analyses of these factors, the area under the curve of HU value of the S1 screw trajectory was the highest (0.79). Measuring the HU value of both the L1 vertebral body and S1 screw trajectory aids in predicting screw loosening.