Aquaponics enhance the sustainability of recirculating aquaculture systems by transferring nutrients from wastewater to plant biomass. However, suboptimal nutrient profiles in aquaculture effluent can affect the quality and safety of aquaponic produce. This study assessed the effects of unfertilized (pure) and fertilized aquaponic nutrition on growth and physiological quality (minerals, vitamins, pigments, antioxidants, organic acids, nitrate), sensory traits, and microbiological safety of butterhead lettuce under two photoperiods (12:12; 18:6). Unfertilized aquaponics resulted in 30 % lower growth (112.2 +- 27.2 g) compared to fertilized (164.4 +- 47.1 g) and hydroponic control (160.7 +- 44.1 g). Under the 12:12 regime, unfertilized aquaponic lettuce was comparable to control, except for altered P, Fe, and Na levels and higher antioxidant capacity (ORAC: 309.5 μM/g DW). Under 18:6, additional differences emerged: dry matter, zeaxanthin, total phenolics, and citrate were affected. Unfertilized aquaponic lettuce showed no significant sensory differences, although this group did not receive any additional nutrient supplementation. The yield of fertilized aquaponics was comparable to hydroponics, suggesting a viable reuse strategy for aquaculture wastewater, achieving, on average, nitrogen savings of 66 %. However, microbial safety remains a concern: Aeromonas spp. were detected on all samples (2.43-5.34 log CFU/g), and Salmonella was found on roots. In fertilized treatments, aerobic plate count and coliform levels on roots exceeded ICMSF limits. To ensure food safety, roots should not be included in packaging, nutrient solutions require regular disinfection, and Good Agricultural Practices (GAP) must be developed and applied.