Sikeston St. Louis, Iron Mountain and Southern Railway Depot, also known as the Sikeston Missouri Pacific Railroad Depot, is a historic train station building located at Sikeston, Scott County, Missouri. It was built in 1916-1917 by the St. Louis, Iron Mountain and Southern Railway, and is a one-story, rectangular brick building measuring 24 feet by 100 feet. It has a hipped, red ceramic tile roof with wide eaves supported by curvilinear brackets. It houses a local history museum.
It was added to the National Register of Historic Places in 2000.