For a study, researchers sought a link between serum inflammatory mediators, preoperative cervical spine illness severity, and clinical outcomes following anterior cervical discectomy and fusion (ACDF). Between 2015 and 2017, all patients over 18 who received ACDF for cervical spondylosis with concomitant radiculopathy and myelopathy at a single hospital were prospectively enrolled. Preoperative serum inflammatory markers like interleukin (IL)-6, IL-8, tumor necrosis factor-α, high-mobility group box-1 (HMGB1), and white blood cells were measured and correlated with patient demographics, surgical characteristics, duration of symptoms, previous opioid use, and preoperative and 1-year postoperative patient-reported outcomes measures (PROMs) like the neck disability index (NDI), visual analog scale neck pain, visual analog scale arm pain, and  Physical and Mental Component Scores of the Short Form-12 (PCS and MCS, respectively) using spearman’s rho coefficient. A total of 77 patients were included, with 62% (n=48) of them receiving follow-up PROMs at least 1 year following ACDF. The absolute amounts of IL-6 and tumor necrosis factor-α were shown to have only a minor correlation (ρ=0.479). Preoperative symptoms that lasted less than 1 year were only weakly associated with an increase in HMGB1 (ρ=0.421). The preoperative inflammatory indicators had no connection with any other patient variables. Greater HMGB1 was modestly linked with lower preoperative PCS (ρ=0.355) and higher preoperative NDI (ρ=0.336). Preoperatively, lower MCS (ρ=0.395) and greater NDI (ρ=0.317) were slightly linked with increased white blood cells. MCS recovery ratio (ρ=0.321) and postoperative improvement in MCS (ρ=0.306) had a weakly positive connection with IL-6. Preoperative cytokine levels showed little association with preoperative complaints or clinical improvement, implying that the patient cytokine profile was of limited use in predicting outcomes after ACDF.