West Nile fever (WNF) is a vector-borne infection caused by a Flavivirus-West Nile virus (WNV). WNV is transmitted by mosquitoes, and birds are the major natural reservoir. A recent increase in the number of the WNF cases has been reported in Europe, the Balkans, and Bulgaria. We herein present the clinical course, laboratory and imaging findings of three patients – a female and two male patients, who were diagnosed with WNF. They were investigated in an epidemiological study, and by using clinical observation, laboratory and microbiological methods, serological tests for specific anti-WNV antibodies detection, molecular biology techniques (polymerase chain reaction, PCR), computed tomography (CT) and magnetic resonance imaging (MRI). The patients presented with fever, headache, drowsiness, and dizziness and anti-WNV antibodies were detected in their serum samples. WNV-RNA was found in a blood sample from the female patient. Both anti-WNV IgM and Herpes simplex virus-1 DNA were detected in a cerebrospinal fluid sample from one of the men. The three patients recovered from the disease after a long convalescent period. WNF has no specific signs, laboratory and imaging findings and could be a life-threatening condition, leading to serious complications. Therefore, WNF should be taken into consideration during the summer when the vector of the infection is active.