There are 15 species of fish known to occur on the Refuge. Arctic grayling, burbot, lake trout, northern pike, and whitefish are present in refuge lakes and rivers. There are no significant salmon runs in the upper Tanana River drainage. However, small runs of chum salmon and an occasional chinook and coho have been recorded.

Humpback whitefish have been the focus of an ongoing study in the upper Tanana River drainage since 1998. This project is designed to test the utility of refined radio telemetry techniques and equipment to track the movements of adult humpback whitefish. Transmitters are surgically implanted in captured fish and their movements monitored using boat and aerial tracking techniques. The methods have been very effective. Following tagging they drop a short distance downstream. In late summer they migrate upstream to relatively discrete regions of the Nabesna and Chisana rivers now known to be spawning areas, where they remain until early October. By winter they drop back downstream into regions of the Tanana River and the Tetlin Lake system, where they stay through spring.