This study compared open-air and semi-enclosed production system of the marine microalgae Nannochloropsis oculata in a sub-tropical region (32°S; 52°W) under uncontrolled environmental conditions. The semi-enclosed system was composed of 1.2 m3 circular tanks installed inside of a greenhouse. Water temperature was 4 °C higher in the indoor treatment than in the outdoor, mainly in winter although no difference was observed in warmer seasons. Moreover, variation in salinity was observed in the outdoor treatment due to rainfall (winter) and evaporation (spring), whereas indoor treatment experienced an increase (up to 100 PSU) due to evaporation only in warmer seasons. Light transmission was approximately 20% lower in the indoor treatment although cell densities and biomass yields were higher indoor during winter. As the temperature increased (spring) no differences were observed among treatments. In summary, partial control of temperature and salinity in the semi-enclosed system, especially during the colder and rainy season, allowed higher microalgae biomass production. Further experiments must be conducted with CO2 addition, larger pH range and salinity control.