The South American sea lion (SASL, Otaria byronia) is one of the species of pinnipeds that display the strongest level of conflict with fishing activities throughout its distribution range. However, little is known about potential temporal and/or spatial variations in the magnitude and effects of SASL and fishing interactions over an entire year and at different sites simultaneously. This study examines the factors that affect the intensity of the operational interaction between SASL and the artisan gillnet fishery in central Chile. Between 2014 and 2016, a total of 145 hauls at three artisan fishing coves were analyzed. South American sea lion interactions were observed in 82 of the 145 (56.6%) hauls analyzed, most frequently at the coves of San Antonio and El Membrillo. From the examined factors, Predation per Unit Effort increased with the number of SASL, however it decreased both during the summer and with greater distance from the nearest SASL colony. Artisan deterrent systems used by fishermen were found to be inefficient in avoiding the interactions with sea lions. Although the intensity of the interaction has increased in recent years (compared with previous studies in the area), the observed Catch per Unit Effort did not differ significantly during fishing trips with or without interaction, indicating that SASL is not a determining factor in the variation of artisan fishery catches. These results demonstrate that the intensity of interactions is not produced at random but rather it is related to factors that obey biological and ecological aspects of the SASL. These factors should be considered for the development of effective actions to prevent, or at least to reduce the interaction between SASL and artisan fisheries.