Condition, growth, and reproductive indices of blue mussels (Mytilus edulis) grown in deep and shallow sites were studied from May to December 2016 in the South Arm region of Notre Dame Bay, Newfoundland. The region was shown to be characterized by a seasonal thermocline that formed in April and lasted to October annually, resulting in a cold-water deep layer (mean annual temperature: 4.36 ± 5.1°C) and a comparatively warmer surface layer (mean annual temperature: 5.81 ± 6.3°C). The deepwater culture sites extended into the cold-water layer and the shallow sites were typically in the warmer layer above. Mussels grown in shallow sites had longer and heavier shells than those from deepwater sites, likely linked to warmer surface waters. Both reproductive and physiological condition indices were high for mussels from both culture depths in May. Physiological condition declined for both deep and shallow cultured mussels from May through to August. Mussels from deep sites, however, had a higher overall mean dry tissue weight: wet tissue weight ratio for the study period. Reproductive indices, including measurements of reproductive output, declined for shallow mussels from May through to August, but remained high for deep mussels until August when a significant spawn occurred for mussels from both depths. In addition, mussels from deep sites were observed to maintain themselves in a prespawning ripe stage for a longer period than those from shallow sites. Variations in physiological and reproductive indices for mussels from each respective culture depth were thought to be linked to differences in the environmental characteristics of the deep and shallow water layers, including rate of temperature change and potential differences in phytoplankton quality and energetics. The additional data provided in the present study add to the current understanding of the effects of the deepwater environment on mussel reproduction patterns and its relationship to production meat yield. The data will help in highlighting the benefits of using deepwater sites leading to increased environmental sustainability for mussel culture in subarctic coastal environments such as those on the north coast of Newfoundland.