<p>Significant seasonal changes in chemical and microbiological water quality can occur in buildings at different fixture locations due to temperature and time dependent reaction rates. Here, a series of calibrated plumbing hydraulic-water quality models were developed for the extensively monitored Retrofitted Net-zero Energy, Water & Waste (ReNEWW) house in West Lafayette, Indiana USA. Knowledge gaps that inhibited higher resolution water quality modeling were also identified. The eight new models predict the absolute level of free chlorine, total trihalomethanes (TTHM), Cu (Copper), Fe (Iron), Pb (lead), NO₃^–(nitrate-nitrogen), heterotrophic plate count (HPC), and <i>Legionella spp.</i> concentration at each fixture for plumbing use, operational characteristics, and design layouts of the plumbing system. Model development revealed that the carrying capacity to describe Legionella spp. growth (and other organisms) under water usage and plumbing design conditions is lacking in the literature. This information needed for higher resolution modeling. Reducing building water use by 25% prompted increased absolute concentrations of HPC and Legionella, each increasing by a factor of about 10⁵. When the service line length was increased, Legionella spp. concentrations increased by up to 10⁶gene copies /L in the Summer season. The proposed modeling framework can be used to support better planning, design, analysis, and operational decision-making.</p>