Recently, Mozambique tilapia (Oreochromis mossambicus Peters, 1852) were listed on the IUCN Red List as near-threatened as their populations are at risk due to hybridization. Another factor that potentially contributes to their population decline is that they are regularly infected by the invasive parasitic copepod anchorworm, Lernaea cyprinacea Linnaeus, 1758. Considering anchorworm-infected Mozambique tilapia are common, understanding their condition with respect to infection is difficult as uninfected fish from the same localities have been unavailable for comparison. A severe drought in southern Africa has created hypersaline environments in the Phongolo River floodplain of north-eastern South Africa, such that freshwater parasites cannot survive and uninfected fish are now found. To determine how infection influences host health, infected and uninfected Mozambique tilapia were collected before and during drought conditions, from Nyamiti pan of the Phongolo River floodplain. Anchorworm-infected fish prevalence was recorded, and anchorworms were collected from hosts and identified to the species level using molecular data of the 18S rRNA gene. For each fish, intensity of anchorworm infection, total length, and weights of the gutted body, liver, spleen, and gonads were recorded. Gutted condition factor, hepato-, spleeno-, and gonado-somatic index values per fish, and prevalence of infection per collection were determined. A rapid health assessment was also conducted to determine a health score for each fish. Molecular analyses confirmed the anchorworm studied was L. cyprinacea. Prior to and during drought, prevalence of infection was 100%, and 0%, respectively. Before drought, fish had significantly reduced hepato-, spleeno-, and gonado-somatic index values, and higher health assessment scores, yet significantly higher gutted condition. Anchorworm intensity was indirectly correlated with fish liver and gonad condition. This study demonstrates that host condition and health varies greatly with respect to drought and infection, and provides the necessary data for follow-up studies in post-drought conditions.