The Parroquial Mayor del Espiritu Santo is one of Cuba's oldest and best-preserved churches. The original church on this site was built in 1522 and made of wood construction but was rebuilt in 1680 in stone. Today the Parroquial Mayor del Espiritu Santo is a Romanesque and baroque design. Its massive bell tower is visible from much of Sancti Spíritus, and though its interior is sparsely decorated—a carved wooden ceiling and a blue-and-gold wooden arch framing a simple altar—it's extremely well preserved. The church is also famous for the sermon of Fray Bartolome de las Casas that he delivered here, and became the beginning of his effort to help the Amerindians.

This spot hosts live-music shows starting at 10 pm Wednesday through Saturday and on Sunday afternoons.

This refurbished 19th-century building overlooks Plaza Serafín Sánchez and the porticos of the colonial buildings that surround it. It's an impressive edifice, with large, arched doorways. Seating is at sturdy wooden tables, a couple of which have views of the Iglesia Parroquial Mayor. The menu is traditional Cuban with a few twists, such as garbanzo mesonero (garbanzo and pork soup) and ternero a la villa (veal stewed in a clay pot).

Between the muddy Río Yayabo and the Calle el Llano, this ancient yellow manor house with a large, tree-shaded terrace is an appealing spot. Seating is available on the terrace, which has a river view, or inside, where the terra-cotta floors, thick columns, and wide arches attest to the building's lifespan of almost three centuries. Specialties are pollo a la quinta (chicken in a vegetable tomato sauce) and vaca frita (strips of beef sautéed with onions), and an array of creole dishes.