Six pyrazole alkaloids of natural origin (isolated from Newbouldia laevis in DR Congo) that exhibit antimalarial activity-namely withasomnine, newbouldine, and their para-hydroxy and -methoxy derivatives-were investigated theoretically. The nitro derivatives of withasomnine and para-hydroxywithasomnine, which show enhanced antimalarial activity, were also studied in this manner. A thorough conformational study was performed in vacuo and in three solvents (chloroform, acetonitrile, and water) at different levels of theory (HF, DFT/B3LYP, and MP2) using different basis sets. Adducts with explicit water molecules were calculated at the HF level. Due to the rigidity of the pyrazole system and the benzene ring, the only factor that influences the energies of withasomnine and newbouldine is the relative orientation of the two ring systems; two orientations are equally preferred. The para-hydroxy and -methoxy derivatives show a preference for a planar orientation of the OH and OC bonds. The main stabilizing influence on the nitro derivative of para-hydroxywithasomnine is the intramolecular hydrogen bond between the two consecutive functional groups. The calculated adducts show the preferred arrangements of water molecules in the vicinity of the N atoms of the pyrazole system and, for the derivatives, also in the vicinity of the substituents on the benzene ring.