Mortality increases during periods of elevated heat. Identification of vulnerable subgroups by demographics, causes of death, and geographic regions, including deaths occurring at home, is needed to inform public health prevention efforts. We calculated mortality relative risks (RRs) and excess deaths associated with a large-scale California heat wave in 2006, comparing deaths during the heat wave with reference days. For total (all-place) and at-home mortality, we examined risks by demographic factors, internal and external causes of death, and building climate zones. During the heat wave, 582 excess deaths occurred, a 5% increase over expected (RR = 1.05, 95% confidence interval (CI) 1.03–1.08). Sixty-six percent of excess deaths were at home (RR = 1.12, CI 1.07–1.16). Total mortality risk was higher among those aged 35–44 years than ≥65, and among Hispanics than whites. Deaths from external causes increased more sharply (RR = 1.18, CI 1.10–1.27) than from internal causes (RR = 1.04, CI 1.02–1.07). Geographically, risk varied by building climate zone; the highest risks of at-home death occurred in the northernmost coastal zone (RR = 1.58, CI 1.01–2.48) and the southernmost zone of California’s Central Valley (RR = 1.43, CI 1.21–1.68). Heat wave mortality risk varied across subpopulations, and some patterns of vulnerability differed from those previously identified. Public health efforts should also address at-home mortality, non-elderly adults, external causes, and at-risk geographic regions.

With climate change, heat waves (HWs) are predicted to increase, particularly in areas where HWs have historically occurred. A multitude of studies have demonstrated that human mortality increases during HWs. California has suffered a number of HWs. The "Great" California HW of July 2006 was unprecedented in duration and occurred statewide, lasting ten days in much of the state and longer in some areas. We calculated the ratio of deaths during the heat wave period (July 15 – Aug 1, 2006) to deaths on non-heat wave days in the same summer. We calculated these rates by California\'s sixteen building climate zones. These zones were outlined in 1982 based on climate, elevation, and estimated energy consumption. HW mortality ratios were higher: i) in the northern coastal zone (a 19% excess of mortality) compared to other coastal zones ofCalifornia (-0.1 to 6% excess); and ii) in the southern and northern zones of the Central Valley (a 11 to 12% excess) compared to the central zone of the Central Valley (a 2% excess). We examined available meteorological, census, and other data, and discuss whether these differences may be related to zonal differences in HW intensity or duration, air conditioning use, building insulation requirements, or other factors such as occupation. Notably, the northern and southern zones of the Central Valley are farming areas. In contrast, the central zone of the Central Valley includes the state capitol, where a higher percentage of workers are office workers. Identifying resilient (low health impact) and vulnerable (high health impacts) zones, and factors that may mitigate the health impact, may ultimately inform climate change mitigation and adaptation policies.