Monkeypox (MPX) is a zoonotic infection caused by an orthopoxvirus that is endemic to Central and Western Africa. The MPX virus is a part of the same family of viruses as the variola virus, which causes smallpox. Since May 2022, there has been a global increase in the incidence of MPX infections in multiple countries where the illness is not usually prevalent. A growing number of publications have emphasized on the need for increased awareness among all health professionals for the rapid recognition and diagnosis of this disease and for proper public health measures. However, atypical presentations and occurrence of uncommon symptoms receive less than the desired attention. More specifically, MPX infection related nociceptive symptoms are currently underexposed. Nevertheless, reports from the current outbreak have revealed that (severe) pain is one of the major causes for distress and even hospitalization in these patients. As for all serious pain conditions, an integrated, multidisciplinary, and holistic approach is indicated. This approach should be multimodal and include non-pharmacological therapies alongside pharmacological approaches. Health care professionals should be aware of available alternatives when first choice analgesic therapies fail. Protocols for identification of pain type and prolonged monitoring of clinical status should be implemented to improve patient well-being during acute infection, but also prevent chronic nociceptive syndromes.