Background <p>Persistent symptoms attributed to tick bites or tick-borne diseases are poorly understood. We estimate regionally adjusted prevalence of persistent symptoms, investigate seroprevalence (IgG) and ongoing infections, and examine associated demographic and clinical factors.</p> Methods <p>Persons aged 18 years or older with persistent symptoms lasting six months or more attributed to tick bites or tick-borne diseases, were recruited into a nationwide cross-sectional study. Demographic data were recorded. Medical records were collected (February 2020 - April 2022) and reviewed for tick bites, tick-borne infections, antibiotic treatment, and clinical findings. Outcome measures included somatic symptoms (PHQ-15), fatigue (Fatigue Severity Scale), physical health (RAND-36), and affective symptoms (HAD Scale). Laboratory assessments included polymerase chain reaction (PCR) analysis of blood samples for <i>Borrelia burgdorferi</i> (Bb) and other known tick-borne pathogens, along with IgG antibody detection.</p> Results <p>The highest prevalence of persistent symptoms attributed to tick bites or tick-borne diseases was found in southwestern Norway (0.152–0.155%); the lowest was in the north (0.033%), which also had significantly lower <i>Bb</i>-IgG seroprevalence (15.4% compared to the national average 37.5%). Symptom persistence was not associated with confirmed tick exposure or tick-borne infection. Somatic symptoms were associated with low physical activity and comorbidity. Fatigue and poor physical health were strongly associated with underemployment. Fatigue was also associated with depressive symptoms, low activity, sick leave, and comorbidities.</p> Conclusions <p>Persistent symptoms were most prevalent in tick-endemic regions but were not associated with prior tick exposure or tick-borne infections. Symptom burden was primarily associated with comorbidities, especially physical inactivity and underemployment.</p> Clinical trial number <p>Not applicable.</p>