UV disinfection is an efficient way to inactivate chlorine resistant protozoan pathogens such as Cryptosporidium parvum and Giardia muris. In the United States, regulatory UV disinfection credit is typically granted when turbidity is <1 NTU. However, studies show turbidity does not correlate well with UV dose responses and partial inactivation when turbidity is > 1 NTU should be considered to avoid certain violations while still protecting public health. The objective of this study was to examine the impact of worst-case scenarios at drinking water treatment plants on UV disinfection. Indigenous spores from unfiltered source water and samples taken during the flocculation and softening steps at the Dublin Road Water Treatment Plant in Columbus, Ohio were exposed to Low-Pressure mercury UV254 disinfection from July 2019 to January 2020. Raw source water and softened water had similar dose responses despite significantly different water quality parameters. Flocculated water had the worst dose response: significantly lower maximum inactivation rate and higher residual population density than the other two water types despite having a lower turbidity than softened water. The modeled Geeraerd-tail maximum inactivation rates (k¬max) were 0.027, 0.021, and 0.030 cm²/mJ for raw source, flocculated, and softened water, respectively. The modeled Geeraerd-tail residual population density values (N¬res) were 1.168, 7.081, and 0.216 SFU/mL for raw source, flocculated, and softened water, respectively. Relationships between water quality parameters and modeled UV inactivation parameters were analyzed to determine and compare other potential indicators for UV disinfection to turbidity. Particle size and particle properties that govern the degree of particle-associated microorganisms best explained the differences in dose response between flocculated water and the other two water types. Larger particles are worse for UV disinfection. Microorganisms associated with particles are harder to disinfect with UV and lead to tailing. Climate change impacts on types, consistency, quantity, and quality of source waters for drinking water treatment make it especially important to understand UV disinfection kinetics under challenging scenarios. Informing regulatory changes to properly account for disinfection when turbidity is > 1 NTU could be especially useful for small or aged utilities that may not be as equipped to handle highly variable water qualities.