Background Patients with strangulation small bowel obstruction are at a high risk for serious morbidity and mortality due to ischemic bowel. Measuring serum, cell-free deoxyribonucleic acid levels could help recognize early cell death. Our hypothesis was that small bowel ischemia or necrosis is associated with increases in serum cell-free deoxyribonucleic acid and that recovery is associated with a decrease in cell-free deoxyribonucleic acid levels. Methods A prospective cohort study in addition to standard treatment of patients admitted with a diagnosis of small bowel obstruction. The participants were divided into groups depending on the presence of ischemic or necrotic bowel according to operative and clinical outcome. Clinical data and serum-based cell-free deoxyribonucleic acid levels were compared. Cell-free deoxyribonucleic acid levels from these 2 groups also were compared with a third group of healthy controls. Results In the study, 58 patients were enrolled, and 18 patients (31%) underwent operation. During the operative procedure, ischemic or necrotic bowel was found in 10 cases (17%). Serum levels of cell-free deoxyribonucleic acid at the time of admission in the ischemic/necrotic bowel group were increased compared with patients with well perfused or spontaneously recovered bowel (P =.03). Cell-free deoxyribonucleic acid levels decreased on the day after admission in 88% of the nonoperated patients. No significant differences were found in demographics, medical background, imaging performed, and cause of obstruction nor in clinical admission data. Conclusion Surgeons currently rely on imprecise clinical parameters, including degree of pain, abdominal tenderness, leukocytosis etc to decide when operative intervention is needed. The association of cell-free deoxyribonucleic acid with small bowel obstruction, ischemia, and recovery supports our hypothesis and suggests that this biomarker is a potential surrogate of small bowel perfusion.