Elevated plasma concentrations of non-esterified fatty acids (NEFA), due to high fat intake and/or adipose tissue lipolysis, are a hallmark of the metabolic syndrome. We assessed whether certain plasma NEFA species contribute to the chronic low-grade inflammatory state seen in the metabolic syndrome. We determined the fasting plasma NEFA patterns of 75 overweight non-diabetic subjects and analysed their relationship with plasma inflammatory parameters. After adjustment for gender, age, body fat, and waist-hip ratio, no strong correlations of single NEFA species with leukocyte number, C-reactive protein, interleukin-6, tumour necrosis factor-alpha, or monocyte chemoattractant protein-1 were detected. However, oleate was negatively (r=-0.36, p=0.0015) and myristate (r=0.41, p=0.0003) as well as the omega3-polyunsaturated NEFA alpha-linolenate (r=0.37, p=0.0011), eicosapentaenoate (r=0.40, p=0.0003), and docosahexaenoate (r=0.40, p=0.0004) were positively associated with interleukin-8 concentrations. The other NEFA species as well as the total plasma NEFA concentration did not correlate with interleukin-8. The correlations of myristate, oleate, and the sum of all omega3-polyunsaturated NEFA with interleukin-8 were independent of plasma tumour necrosis factor-alpha and overall adiposity. Our data demonstrate close and selective associations of oleate, myristate, and omega3-polyunsaturated NEFA with plasma concentrations of the pro-inflammatory chemokine interleukin-8. Thus, these NEFA species may represent specific determinants of plasma interleukin-8.