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The goliath frog (Conraua goliath) is an Endangered species exclusively found in Cameroon and Equatorial Guinea. Climate change, deforestation and overhunting are principal causes driving this species to extinction. Therefore, a better understanding of the genetic diversity and population structure of this species is necessary to improve conservation efforts. Here we used two mitochondrial genes (Cytochrome Oxidase subunit 1 (COI) and 16S) extracted from 54 C. goliath individuals from six localities in Cameroon to examine their genetic diversity. The result shows a low DNA substitution between the sequences. There were four 16S and two COI haplotypes in total. Overall, genetic diversity was very low for all the genes with nucleotide diversity of 0.00106 and 0.00007 for 16S and COI respectively. The Tajima D and Fu Fs statistics were negative. The TCS haplotype network revealed a predominant and ancestral haplotype (H1) for these genes which is distributed in the 6 populations. Pairwise genetic differentiation (F-ST) generated between these populations using 16S revealed very high differentiation between populations from Nkam and Mungo Administrative Divisions in Cameroon. In contrast, we observed low differentiation among the geographically clustered Mungo and Nkam populations. Overall, human activities and perhaps climate change can appear to have depleted genetic diversity in the scattered populations that remain of this amphibian. To sustain the Goliath frog, we suggest to the Cameroonian government to implement more effective strategies to conserve and manage remnant populations of this iconic species through more effort against poaching which contribute to reduce the genetic diversity.