Pneumocystis jirovecii pneumonia (PCP) is an opportunistic fungal infection that has traditionally affected immunocompromised patients, particularly those with HIV. However, a rising trend in PCP cases has been observed among patients without HIV, including those with autoimmune diseases, malignancies, and long-term immunosuppressive therapies. This study examined the characteristics of patients diagnosed with PCP over a 5-year period in a UK hospital, aiming to reaffirm known disease risk factors. The findings highlight the increasing prevalence of PCP in non-HIV populations, particularly those with autoimmune and rheumatological conditions, and the importance of considering PCP prophylaxis in high-risk patients on long-term immunomodulating therapies. However, the lack of robust evidence regarding the benefits of prophylaxis and the challenges in diagnosing PCP in non-HIV patients, such as the infrequent use of diagnostic tests, require further research to develop more comprehensive risk assessment tools and targeted prophylaxis strategies.