The effect of chronic intestinal trematode infection on malaria was examined in a murine model of co-infection using Echinostoma caproni and Plasmodium yoelii. BALB/c mice (n = 32) infected with a low dose of E. caproni (∼10 cysts) 25–35 days before malaria infection displayed significantly increased malaria parasitemia (P = 0.01), extended patency of malaria (P = 0.03), and increased fatality (47%; P < 0.001) compared to mice infected only with P. yoelii (17X nonlethal strain) (n = 18). Further analysis revealed that differences in malaria parasitemia between fatal co-infections and infections with P. yoelii only were highly significant (P < 0.0001), whereas nonfatal co-infections were not statistically different. Exacerbation of malaria was demonstrated to be reversible through clearance of E. caproni worms by praziquantel treatment administered 10 days before malaria infection. No deaths were observed during malaria infection in mice cleared of their E. caproni infection (n = 10), and parasitemia was significantly reduced from that of untreated co-infected mice (P = 0.03) and was not different from that of mice infected with P. yoelii only. Further studies examining parasite-parasite interactions and host immune response in the echinostome model are warranted to understand the mechanisms affecting the course and outcome of malaria infection during concomitant helminth infection.