In normal subjects, elevation of plasma free fatty acid (FFA) levels stimulates gluconeogenesis (GNG) and inhibits glycogenolysis (GLY). In adults with uncomplicated Plasmodium falciparum malaria, GNG is increased and GLY decreased. To test the hypothesis that FFAs are regulators of GNG and GLY in uncomplicated falciparum malaria, 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, six matched healthy subjects were studied on two occasions with and without acipimox. After 16 h of fasting, glucose production and GNG were significantly higher in the malaria patients compared with the healthy controls (P = 0.003 and < 0.0001, respectively), whereas GLY 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 statistically significant difference between the acipimox-treated and untreated patients. In controls, however, with acipimox the decline was less outspoken compared with nontreated 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, GLY 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 regulation of glucose production, nor of GNG or GLY.