Stable isotopes of carbon and oxygen in tree-ring cellulose are useful for elucidating tree physiological responses to environmental conditions.  We examined d¹³C and d¹⁸O of tree-ring cellulose from Quercus rubra (L.) in the Midwestern US.  We examined apparently healthy and declining trees, across multiple decades (1964 to 1994) encompassing relatively wet and drought periods.  We tested the hypothesis that both isotope ratios decrease with increasing moisture availability, as predicted by theory.  Tree-ring cellulose d¹³C values ranged from –25.7 to –22.4‰ and d¹⁸O values ranged from 26.9 to 31.0‰.  Both d¹³C and d¹⁸O experienced this range of values during drought periods; during wetter years, the range of values were smaller, spanning ~1.2‰ and ~1.4‰ for d¹³C and d¹⁸O, respectively.  Tree-ring cellulose d¹³C declined with tree age, regardless of drought status, contrary to expectations, and d¹⁸O exhibited no relationship with drought.  The relationship between d¹³C and d¹⁸O was significant and positive, with r² values ranging from 0.53 to 0.96 for categories describing tree health and drought severity.  During a severe drought in 1981-1983, tree-ring cellulose became relatively ¹³C-deplete, while d¹⁸O declined.  The apparent maintenance of physiological functioning as exhibited via d¹³C in conjunction with the decline in d¹⁸O during this drought suggests that all trees, regardless of apparent health status, accessed water from relatively deep within the soil profile compared to other time periods.  As a result, neither d¹³C nor d¹⁸O exhibited a relationship with drought severity, contrary to theory.  Variation in d¹⁸O was at least as significant as that in d¹³C, suggesting that source water d¹⁸O governed tree-ring cellulose d¹⁸O, not evaporative enrichment, in contrast with a recently published study.  These data indicate the extent to which responses to environmental cues of d¹³C and d¹⁸O from non-phreatophytic trees may be mitigated when they can access deeper soil water.