Anemia is one of the severe clinical outcomes associated with concomitant infection of malaria and soil-transmitted helminths (STH). Since STH infections mostly share similar geographical areas with malaria, the influence of co-infections on the epidemiology and course of Anemia deserves greater consideration to assess the impact of interventions, the adequacy of strategies implemented, and the progress made in the fight against Anemia. So, this study was done to investigate Anemia among STH-negative malaria patients and malaria patients co-infected with single or multiple STHs, in 3 health facilities of Arba Minch, 2020 to 2021. An institutional-based comparative cross-sectional study was conducted at 3 Governmental Health Institutions, Arba Minch, and southern Ethiopia from November 2020 to February 2021 on a total of 321 malaria-positive study participants. Thick and thin blood films were prepared for microscopic examination of malaria parasites and identification of species. A malaria parasite count was done to determine the intensity of the infection. A stool wet mount was done to identify STHs. Kato-Katz was done for microscopic quantitative examination of STHs. A complete blood cell count was done to determine hemoglobin level. Socio-demographic data were collected using a questionnaire. Data were analyzed using SPSS version 25. Independent samples t test and one-way analysis of variance were done. Anemia magnitude in this study was 38.3% and it was higher in malaria with multiple STH co-infection groups (55.1%). Malaria parasite density was significantly higher in malaria with multiple STHs co-infected study participants F (2, 318) = 20.075. It increased with the increasing intensity of hookworm, Trichuris trichiura, and several co-infecting helminth species. But it decreased with increasing intensity of Ascaris lumbricoides. The mean hemoglobin concentration of malaria with multiple STHs co-infection study participants was significantly lower than mono malaria-infected and malaria with single STHs co-infection study participants. The management of malaria should take account of STH infections and optimal modalities of treatment should be devised. Anti-helminthic treatments of malaria patients through regular, inexpensive, single-dose, and highly effective drugs must be seriously considered to protect the population from exacerbation of Anemia by intestinal helminth infections.