The results of a study on the deactivation of an industrial Co–Al2O3/SiO2 catalyst under the conditions of highly productive Fischer–Tropsch synthesis of long-chained hydrocarbons at high pressure (6 MPa) are presented. It was found that an increase in the synthesis temperature led to a decrease in the rate of catalyst deactivation. The effect of the thermal agglomeration of cobalt particles and the carbonization of catalyst surface on the activity of the catalyst under the test conditions was insignificant. A correlation between the rate of catalyst deactivation and the selectivity for С19 hydrocarbons was found; this correlation indicated the blocking of chain growth centers by synthesized waxes as the main reason for the rapid loss of catalyst activity.