Background <p>Although vitamin D deficiency has been linked to adverse outcomes in critically ill patients, its impact on sepsis-related short- and long-term complications, particularly skeletal sequelae, remains poorly understood. This study aimed to investigate the long-term bone metabolism outcomes in patients with sepsis and its association between vitamin D status.</p> Methods <p>A retrospective baseline data collection and two prospective cohort analyses (with 5-year follow-ups) were conducted using data from 400 adults (18–70 years) admitted to the ICU (2008–2018) at the First Affiliated Hospital of Xi’an Jiaotong University in China. We first compared septic patients and non-septic patients, observing the relationship between sepsis and vitamin D levels. Next, we identified the long-term outcomes (osteoporosis) of patients after sepsis. Additionally, patients with sepsis were stratified into two cohorts based on baseline vitamin D levels. The outcomes in this cohort included all-cause 60-day mortality, and bone loss (osteoporosis). We conducted a statistical analysis using a 1:1 propensity score matching (PSM) to adjust for potential confounding variables.</p> Results <p>A total of 400 patients were included in the study, of whom 214 were diagnosed with sepsis. Patients with sepsis were more likely to have lower serum 25(OH)D levels than non-sepsis subjects (12.6 ± 7.5 vs. 15.5 ± 7.7 ng/mL, <i>P</i> = 0.01). In assessing long-term outcomes, sepsis patients reflected a higher risk of developing osteoporosis than non-sepsis patients (62.2% vs. 16.6%, <i>P</i> = 0.01). Lower vitamin D levels after sepsis were also associated with a higher incidence of osteoporosis (<i>P</i> &lt; 0.01).</p> Conclusions <p>Vitamin D deficiency was a common finding during sepsis. In terms of long-term outcomes, the incidence of osteoporosis within 5 years of hospitalization was higher in sepsis patients, especially in patients with lower Vitamin D levels.</p>