Ethnopharmacological relevance: Lippia multiflora is a plant with nutritional and pharmaco-therapeutic properties that is native to central and occidental Africa. The potential effects of plants on health are associated with their chemical composition. Therefore, the present study aimed to identify chemical variations in essential oils of Lippia multiflora as a function of geographic origin and time of annual harvest to determine optimal chemical profiles for ethno-pharmacotherapeutic applications. Materials and methods: Experimental plants were cultivated at Abidjan (LPA), Toumodi (LPT) and Bondoukou (LPB). Natural Lippia multiflora seeds were sourced to produce standardized plants over a period of six months. Standard plants (n=40) were re-introduced into natural plots, cultivated for 12 months and leaves were sampled monthly in a standardized fashion. Essentials oils (n=36) were then extracted from these samples by hydro-distillation according to the European Pharmacopoeia and qualitatively and quantitatively analyzed using GC/FID and GC/MS. These data were then analyzed using Principal Component Analysis (PCA). Anti-inflammatory properties were also assessed against activated macrophages in vitro. Results: The results indicated that chemical profiles and essential oil yields vary according to the location where the plants were cultivated. One essential oil chemotype corresponded to the LPA and LPT sites and one corresponded to the LPB site. Statistical analysis of the chemical profiles and monthly evolution of the three sites over a period of one year allowed assessment of variations in composition and the subsequent choice of the optimal harvest time for ethnopharmacological applications. Anti-inflammatory activity apparently correlated with chemical profiles of essential oils and the geographic origins of the plants. Conclusion: The optimal harvest time was associated with the maximum yield of pharmacological compounds with the most potential interest for health.