Production of lettuce (Lactuca sativa) within vertical farms is an expanding segment of controlled environment agriculture-precise manipulation of environmental parameters including mean daily temperature (MDT) and carbon dioxide (CO2) concentration enables year-round production, alongside color, yield, and crop size regulation. Our objectives included 1) quantify how MDT and CO2 interact to influence lettuce growth, development, and quality; 2) model lettuce growth under several MDTs and CO2 concentrations. Green butterhead 'Rex' and red oakleaf 'Rouxai RZ' seedlings were transplanted into hydroponic tanks under a photosynthetic photon flux density of 300 mu mol.m(-2).s(-1) for 17-h.d(-1). CO2 concentrations of 500, 800, or 1200 mu mol.mol(-1) and day/night and MDT setpoints of 22/15 degrees C (MDT 20 degrees C), 25/18 degrees C (23 degrees C), or 28/21 degrees C (26 degrees C) were maintained within growth chambers. 'Rex' fresh mass increased linearly with MDT, increasing by 18% from 20 to 26 degrees C. 'Rouxai RZ' fresh mass increased quadratically with MDT, with a 32% increase from 20 to 23 degrees C, then a 7% increase from 23 to 26 degrees C. Elevating CO2 concentrations from 500 to 800 mu mol.mol(-1) increased 'Rouxai RZ' and 'Rex' fresh mass by 33 and 16%, respectively, while fresh mass did not increase from 800 to 1200 mu mol.mol(-1). Both cultivars had the greatest dry mass at 800 mu mol.mol(-1) CO2 across temperatures. At a high MDT, 'Rouxai RZ' foliage color became more light, vibrant, and green, while a low MDT induced darker, grayer, and redder foliage. Tipburn occurred on 'Rex' across treatments, while 25% of 'Rouxai RZ' were afflicted at 500 mu mol.mol(-1) CO2 and 67% at 1200 mu mol.mol(-1). At the light intensity studied, we recommend growing 'Rex' and 'Rouxai RZ' at an 800 mu mol.mol(-1) CO2 concentration and MDT of 23 degrees C for greatest biomass and leaf number, and slightly redder foliage in 'Rouxai RZ' than at a 26 degrees C MDT.