Background: In normals, elevation of plasma free fatty acids (FFAs) levels stimulates gluconeogenesis (GNG) and inhibits glycogenolysis (GL). In adults with uncomplicated Plasmodium falciparum malaria GNG is increased and GL decreased . Aim of the study: To test the hypothesis that FFAs are regulators of GNG and GL in uncomplicated falciparum malaria . Study design: We investigated the effect of inhibition of lipolysis by acipimox in 12 patients with uncomplicated falciparum malaria. Six of them were given acipimox and six served as controls. Also as controls, 6 matched healthy subjects were studied on 2 occasions with and without acipimox. Results: After 16 hours of fasting, glucose production and GNG were significantly higher in the malaria patients compared to the healthy controls (P=0.003 and <0.0001 resp.), while GL was significantly lower (p<0.001), together with elevated plasma concentrations of cortisol and glucagon. During the study, glucose production in patients declined over time (p<0.0001), without a statistical significant difference between the acipimox treated and untreated patients. In controls, however, with acipimox the decline was less outspoken compared to non-treated controls (p=0.005). GNG was unchanged over time in patients as well as in healthy controls and no influence of acipimox was found. In patients, GL declined over time (p< 0.001), without a difference between acipimox treated and untreated patients. In contrast, in controls treated with acipimox no change over time was found, which was statistically different from the decline in untreated controls (p=0.002). In conclusion, in falciparum malaria, FFAs are not involved in regulating of glucose production, neither regulating of gluconeogenesis nor glycogenolysis.