Spruce Run is a tributary of Little Fishing Creek in Columbia County, Pennsylvania, in the United States.

More than 80 species of woodland herbs and numerous trees, mammals, and birds inhabit the area near the stream.

Spruce Run begins in a valley in northern Madison Township, approximately 1 mile (1.6 km) south of the Columbia/Lycoming county line.

Over the next few miles, the stream's valley gets broader and shallower and eventually it stops flowing parallel to Spruce Run Road.

[1] Spruce Run joins Little Fishing Creek 5.87 miles (9.45 km) upstream of its mouth.

There are no all-terrain vehicle trails along the stream and the Columbia County Natural Areas Inventory opposes the addition of any.

[7] The Columbia County Natural Areas Inventory advises against logging on Spruce Run.

[5] However, invasive plants such as the multiflora rose and the autumn olive also inhabit the area near the stream.

These include white-tailed deer, black bear, ring-necked pheasant, cottontail rabbit, wild turkey, and squirrels.