Strong variation in plant organic compound 82H and 818O values such as leaf waxes or cellulose among species is commonly observed; however, the extent to which this isotopic variation is driven by leaf water or biochemical isotope effects is relatively unknown. Therefore, we compared variation in leaf water and organic compound 82H and 818O values (cellulose -82H and 818O, and n-alkanes -82H) across 192 species grown in a botanical garden to assess covariation of isotope values (1) between elements in a given compound, (2) between different (organic) compounds of a given element, and (3) across different growing seasons. Our results suggest that variation in leaf water 82H values are likely not a strong driver for the observed variation in organic compound 82H values across species, and that this may also be true for 818O values. Furthermore, even though correlation between leaf water 82H and 818O values appears to be transferred to organic compounds, the explanatory power of this correlation is strongly diminished (R2 < 0.04). This indicates that additional biochemical isotope fractionation leads to sub-stantial variation in organic compound 82H and possibly also 818O values across species. Moreover, the low explanatory power of the correlation between cellulose and n-alkane 82H values (R2 = 0.06) suggests that the biochemical pathways associated with the different compounds are accompanied by different isotope effects. Lastly, cellulose 82H and 818O values appeared sensitive to environmental differences between growing seasons, while differences in model-predicted source water 818O and 82H values and also climate were negligible between years. By contrast, the species pattern in n-alkane 82H values was highly conserved between the two years. This indicates that the environmental forcing effects on isotope values were not equal between compounds. Therefore, we conclude that variation in organic compound 82H (and possibly also 818O) values among species and growing seasons was more strongly driven by biochemical isotope fractionation rather than by isotope values of plant water. This should be considered in the application of organic compound 82H and 818O values to reconstruct past climate, where invariable biochemical isotope fractionation is often assumed. Alternatively, organic compound 82H and 818O values could be further developed into a tool to extract plant metabolic information.