BackgroundMalaria ranks among the foremost health issues facing the world, especially tropical countries as it is still the no one killer disease in sub‐Saharan Africa. Its endemicity keeps threatening health delivery services in Nigeria as well as other countries though it is in principle a preventable and treatable condition. Elele in Rivers state records one of the highest malaria cases in the country. Malaria has impacted negatively on the economy with about 132 billion naira lost to malaria as cost of treatment and loss in man‐hours.PurposeThe present study evaluated the pattern of parasitological response and symptoms clearance in patients treated with Artemether‐Lumefantrine combination (ALC) in the treatment of uncomplicated malaria in Elele, a malaria endemic area in Rivers State Nigeria.MethodThis study was done at the Madonna University Teaching Hospital and it's out station, Our Saviors Hospital Elele Rivers State Nigeria which is in a high malaria endemic area. It is cross‐sectional descriptive study in which the participants were recruited longitudinally. In the study, parasitological response and symptom clearance in these malaria patients on treatment with ALC were assessed. Laboratory investigation to confirm parasitemia employed two methods including Immunoassay examination (Rapid test), which entails the detection of malaria antibodies in a human blood or serum and microscopic examination, which entails looking for the parasite in a drop of blood under the microscope. Qualitative study using in‐depth interviews (IDIs) and focus group discussions (FGDs) were used to assess their knowledge of malaria infection, its treatment and to obtain socio demographic data. Parasite clearance and symptoms disappearance was determined in the patients taking the above regimen on days 0, 2, 4, 6, 8, 10, and 14.ResultsThe symptoms disappeared in the course of treatment such that by day 6 only 5 patients had fever but no patient had fever by day 10. 60 patients had body weakness by day 6 while only 40 patients had body weakness by day 10. No patient complained of body weakness by day 14. On day 6, only 20 patients had headache, by day 10 only 2 patients had headache. No patient had headache by day 14. The parasite clearance was such that by day 8, there was no detectable parasite in those with mild (+) parasitaemia on day 0. By day 8, 3 patients, (3%) who had moderate (++) parasitaemia on day 0, still had detectable malaria parasites (+); while 1 of the patients, (1%) who had severe (+++) on day 0, still had detectable malaria parasites (+). By day 10, only 1 patient each of moderate (++) and severe (+++) parasitaemia on day 0, still had detectable malaria parasites (+). No parasite was detected in any patient by day 14. By day 14, there was adequate clinical and parasitological clearance (ACPR) in the 100 patients, 100%; p <0.05.ConclusionMalaria infection impacts negatively in the life of people leaving in its endemic areas. All hands must be on deck to help protect the current WHO recommended Artemether‐Lumefantrine Combinations from parasite resistance.Support or Funding InformationNone