The Humboldt River, in northern Nevada supplies water mostly for irrigation of nearby croplands. Groundwater pumping both near and distant from the river has increased over the past 50 years. The primary use of groundwater is for irrigation of croplands but it is also an important source for municipalities, mining and other industries. Large gold deposits that require dewatering were discovered in the mountains of the central part of the drainage basin in the 1970’s and 1980’s. Much of the water pumped to dewater the mines is recharged back to groundwater in the valleys or is released to the Humboldt River or one of its tributaries. Of concern is the long-term loss of groundwater from pit-lake evaporation and how those losses could affect groundwater interactions with the Humboldt River once mine operations cease. Flows in the Humboldt River are mostly dependent on snowmelt runoff from the mountains, particularly from mountains in the drainage area upstream of the Palisade gaging station. The mean flow increases with drainage area between the gaging stations upstream of Elko and at Palisade, whereas the mean flow decreases downstream of the Palisade gaging station. Much of the decrease in mean flow downstream of Palisade is caused by: (1) minimal additional contributions from runoff and groundwater flow; (2) spreading of water to native pastures on the floodplain; and (3) infiltration of river water into its associated alluvium. During low-flow periods, particularly during periods of drought, the Humboldt River between Battle Mountain and Comus gaging stations often has flows less than 1 cubic foot per second (cfs) even before there was any mine dewatering. Estimated groundwater loss to evaporation for the five largest pit lakes in the drainage area between the Palisade and Comus gaging stations is about 5,400 acre-feet per year (afy) (7.6 cfs or five times less than the estimated net annual evaporation loss from the Rye Patch and the Pitt-Taylor Reservoirs upstream of Lovelock, Nevada. The groundwater loss to three of the pit lakes (Goldstrike Mine, Cortez operations, and Twin Creeks Mine) is unlikely to affect river flow because even prior to mine dewatering, groundwater flow from the low-lying mountains was lost to evapotranspiration near the base of the alluvial fans and did not contribute flow to the river. The Lone Tree Mine ceased dewatering in December 2006 and since then a lake has formed in the pit. The floodplain of the Humboldt River in the reach between Battle Mountain and Comus is underlain by a layer of blue clay at shallow depth. Between 2007 and 2019, the net mean annual streamflow loss between Palisade and Comus is nearly the same as during a period of little groundwater pumping from 1946 to 1969 suggesting that even the relatively large amount of water pumped from the mine has had a little effect on Humboldt River flows. Groundwater evaporation from the eventual pit-lake at the Gold Quarry Mine is estimated at 740 afy (about 1 cfs) and could perhaps decrease the gain in the Humboldt River upstream of Palisade. How much of a decrease is uncertain because some of it could be lost to evapotranspiration at the edge of the floodplain prior to reaching the river. Even if the groundwater loss from the pit lake at Gold Quarry Mine were to reduce the gain of river flow between Carlin and Palisade, the loss would be too little to measure accurately.