Many of the systemic manifestations of chronic obstructive pulmonary disease (COPD) are mediated through increased systemic levels of inflammatory proteins. We assessed the long term repeatability of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) over one year and examined the relationships between these systemic markers in COPD. Fifty-eight stable COPD patients completed a baseline and one-year visit. Serum IL-6, plasma CRP, and plasma TNF-alpha were measured. Repeatability was expressed by intraclass correlation coefficient (R(i)) and the Bland-Altman method. Pearson correlations were used to determine the relationships between the systemic markers at both visits. There was moderate repeatability with a very high degree of statistical significance (p <or= 0.001) between the two visits for all the systemic biomarkers (IL-6, CRP, and TNF-alpha). CRP was significantly associated with IL-6 at both visits (r = 0.55, p = 0.0001, r = 0.51, p = 0.0002, respectively). There were no other significant associations between the systemic markers at either of the visits. Systemic inflammatory biomarkers IL-6, CRP, and TNF-alpha were moderately repeatable over a twelve month period in COPD patients. We have also shown that a robust and repeatable association between IL-6 and CRP exists.