Increasing habitat fragmentation leads to wild populations becoming small, isolated, and threatened by inbreeding depression. However, small populations may be able to purge recessive deleterious alleles as they become expressed in homozygotes, thus reducing inbreeding depression and increasing population viability. We used genome sequencing of 57 tigers to estimate individual inbreeding and mutation loads in a small-isolated, and two large-connected populations in India. As expected, the small-isolated population had substantially higher average genomic inbreeding (FROH=0.57) than the large-connected (FROH=0.35 and FROH=0.46) populations. The small-isolated population had the lowest loss-of-function mutation load, likely due to purging of highly deleterious recessive mutations. The large populations had lower missense mutation loads than the small-isolated population, but were not identical, possibly due to different demographic histories. While the number of the loss-of-function alleles in the small-isolated population was lower, these alleles were at high frequencies and homozygosity than in the large populations. Together, our data and analyses provide evidence of (a) high mutation load; (b) purging and (c) the highest predicted inbreeding depression, despite purging, in the small-isolated population. Frequency distributions of damaging and neutral alleles uncover genomic evidence that purifying selection has removed part of the mutation load across Indian tiger populations. These results provide genomic evidence for purifying selection in both small and large populations, but also suggest that the remaining deleterious alleles may have inbreeding associated fitness costs. We suggest that genetic rescue from sources selected based on genome-wide differentiation should offset any possible impacts of inbreeding depression.