The Mascoma River enters the lake near its halfway point, from the northeastern side, at the town center of Enfield.

Recent studies suggest that significant exposure to high levels of cyanobacteria producing toxins such as BMAA can cause amyotrophic lateral sclerosis (ALS).

People living within half a mile of cyanobacterially contaminated lakes have had a 2.3 times greater risk of developing ALS than the rest of the population; people around Lake Mascoma had an up to 25 times greater risk of ALS than the expected incidence.

[2] In June 2009 the State of New Hampshire discouraged people from recreation in some areas of the lake because of the bloom.

NASA and its partners have used the frozen lake to test a robotic rover as a simulation of Antarctica.