If surgical closure of chronic wounds is an option, choosing an appropriate time to definitely close these wounds remains a challenge. Although the underlying mechanisms of nonhealing are not completely understood, serum C-reactive protein (CRP) and interleukin-6 (IL-6) in wound fluid have been found to be markers of the systemic and local inflammation state of chronic wounds. The purpose of this prospective, descriptive pilot study was to evaluate the effect of debridement, systemic antibiotics, and negative pressure wound therapy (NPWT) on the outcomes of trauma-related chronic wounds and changes in local inflammation responses, measured using CRP and IL-6 levels as indicators of cytokine regulation. Between June 2012 and May 2013, 20 consecutive patients (14 men, six women, mean age 40 [range 17-561 years) with various trauma-related, nonhealing chronic wounds were enrolled in the study after failing to heal for an average of 8.5 (range 6-16) weeks using a protocol of regular debridement and gauze dressings. Before the start of the study, wounds were cultured, and laboratory values for white blood cell count (WBC), neutrophils, and levels of serum CRP and IL-6 in the wound fluid obtained. Wounds were surgically debrided and NPWT (continuous at 125 mm Hg) applied. All patients were prescribed systemic antibiotics, and mean time interval between NPWT dressing changes was 5 (range 3-7) days. During an average mean NPWT treatment time of 13 (range 5-20) days, CRP and IL-6 concentrations decreased from 66.4 mg/L to 10.4 mg/L and 44.1 pg/mL to 8.6 pg/mL, respectively (P <0.001). The presence/absence of bacteria, WBC, and neutrophil counts did not change. No complications were noted, and all wounds were successfully closed using various surgical procedures. In this study, clinical wound improvement and a significant decrease in wound fluid CRP and IL-6 levels were observed. Studies with a larger sample size and a more robust study design may help elucidate the relationship between inflammatory molecules, infection, and healing outcomes.