Two new species of Cardicola (Digenea: Sanguinicolidae) are described from the heart of drums (Perciformes: Sciaenidae) in and off Mississippi and Louisiana. Cardicola palmeri n. sp. infects the black drum, Pogonias cromis, and, in mature individuals, is distinguished from its congeners by the combination of a body 1.9–2.9 times longer than wide, an esophagus 44–52% of the body length, posterior ceca 1.0–1.8 times longer than the anterior ones, a gland encircling the seminal vesicle that is 30–37% of maximum body width in diameter, and a sinistral and nearly medial male pore. Cardicola currani n. sp. infects the red drum, Sciaenops ocellatus, and is distinguished from its congeners by the combination of posterior ceca 1.8–4.2 times longer than anterior ones, a male pore located well posterior to the ootype, a female pore and transverse metraterm located just anterior to the level of the ootype, and a medial and posttesticular ovary located at the level of the terminal ends of the posterior ceca. No adult blood fluke had been described previously from the northern Gulf of Mexico west of Florida. Each of the 2 flukes infected only 1 host species despite the hosts being sympatric.