Sacha inchi oil (SIO) is an attractive source of polyunsaturated acids oil. A randomized crossover clinical trial was done to evaluate SIO effects on postprandial lipids and inflammatory state caused by a high-fat intake. Twenty metabolically healthy (MH) and 22 metabolically unhealthy (MU) subjects consumed a high-fat breakfast alone or supplemented with SIO. The biomarkers were measured in serum upon fasting, and after 1 and 4 hrs after breakfast. Interleukin-6 (IL-6) expression was determined in mononuclear cells. In the MH group, SIO reversed the cholesterol increase [iAUCHFM : 0.27 mmol/L/4 h (IQR: -0.07/0.81); iAUCHFM+S : -0.18 mmol/L/4 h (IQR: -0.49/0.31) p = 0.037] and decreased interleukin-6 concentration. In MU group, SIO attenuated lipopolysaccharides increase and interleukin-6 expression [(FCHFM  = -1.19 (IQR: -1.72/1.93) and FCHFM+S  = -1.83 (IQR: -4,82/-0.01), p = 0.017]. The effects of a high-fat meal on postprandial lipids and inflammation could be modified by the addition of SIO, but the outcomes are depending on the metabolic individual status. PRACTICAL APPLICATIONS: The seeds of Plukenetia volubilis L., also known as Sacha inchi, Sacha peanut or Inca peanut are an attractive vegetable source of oil which includes a high content of polyunsaturated fatty acids. Furthermore, the intake of Sacha inchi oil could improve the postprandial responses of a high-fat intake, and could be able to help to prevent cardiovascular diseases. Our results contribute to know the effects of this oil on postprandial inflammation and lipids. In addition, establishing how a person's basal metabolic status can determinate the metabolic response to this oil can help improve its use, and our results add evidence about the role of nutrition and diet in health and disease. At this time, the cultivation of Sacha inchi is being proposed as an agro-industrial alternative for the improvement of quality of living in Colombian rural areas.