The main problem in the flotation of Cu-Mo sulfide ores in seawater is poor floatability of molybdenite at pH>9.5. Froth stability plays a very important role in determining concentrate grade and recovery in flotation operations and in this paper both floatability and frothability have been tested. The frothability have been studied by measuring froth equilibrium layer thickness in a modified laboratory flotation cell. Two chemical aspects of seawater need to be considered: the content of NaCl (around 87% of salinity), and the concentration of secondary ions (around 13%) (sulfate, magnesium, calcium, bicarbonate ions, etc.). Seawater, NaCl solutions, and seawater’s ions were found to depress frothability. The effect of pH on frothability over the pH range from 9.5 to 11, which is very strong in freshwater, becomes negligible in seawater and the tested electrolyte solutions. The analysis of the relationship between the mechanisms of molybdenite depression and the loss of frothability in seawater implies that the effects of the studied ions on molybdenite floatability and on pulp frothability are different. While depression of molybdenite floatability could be tracked down to magnesium hydroxide precipitation as a main culprit, the depression of frothability is a much more complicated issue.