The incidence of postoperative spinal infection (PSI) ranges from 0% to 10%, devastatingly affecting the patient prognosis and increasing costs to the healthcare system because of higher morbidity. Postoperative spinal infections require a high level of suspicion as they are difficult to diagnose, especially in the early postoperative state, because of many confounding factors such as clinical symptoms, serum biomarkers rise or confusing imaging studies. Current research has focused on serum biomarkers at the early stages of disease, nevertheless, most rely on retrospective cohorts with serum biomarkers studied individually and at different time points. To determine the Inflammatory biomarkers behavior profile among patients following elective degenerative spine surgery and their differences with those coursing with postoperative spinal infection. The proposed systematic review will follow the PRISMA statement. This protocol was registered at PROSPERO on January 19th, 2022, obtaining the following register CRD42022304645 on February 19th, 2022. We will include studies related to biomarkers in adult patients operated on because of degenerative spinal diseases, and those developing a postoperative spinal infection. The following information will be extracted: (1)study title; (2)Study Author (3)year; (4)evidence-level; (5)Research-type; (6)diagnosis group (elective postoperative degenerative disease / PSI); (7a)region (Cervical, Thoracic, Lumbosacral, Coccigeal); (7b)Type of infection by anatomical or radiological site, (8)Surgery-Type (including instrumentation or not); (9)number of cases; (10)mean age or individual age; and (11) individual serum biomarker values from the preoperative state up to 90 days postop for both groups including: (10a)interleukine-6, (10b)Presepsine, (10c)Erythrocyte Sedimentation Rate, (10d)Leukocyte Count, (10e)Neutrophil Count, (10f)C-Reactive Protein, (10g)Serum Amyloid, (10h)White Cell Count, (10i)Albumin, (10j)Prealbumin, (10k)Procalcitonin, (10L)Retinol associated protein, (10M)Dickopf-1, (11)postoperative days at symptoms or diagnosis, (12)Type of organism, (13)day of starting antibiotics, (14)duration of treatment and (15)any biases (including comorbidities, especially those affecting immunological status). All biomarkers' data will be presented graphically over time. Figure 1 contains the flow diagram of the methodology. No ethical approval will be required, as this review is based on published data and does not involve interaction with human participants. The search for this systematic review commenced in February 2021, and we expect to publish the findings in middle 2023. The present study will provide the biomarkers' behavior profile for PSI and patients following elective surgery for degenerative spinal diseases from the preoperative period up to 90 days postoperative providing cut-off values at the day of diagnosis. It will provide clinicians with a better background to diagnose based on highly trustable information based on cut-off values from this systematic review. Finally we expect this review to provide a basis for future research on biomarkers to establish more accurate and timely diagnosis in the early stages of illness ultimately impacting the patient's physical and mental health, reducing the disease burden. PROSPERO register ID: CRD42022304645.