## 1 Introduction  
Pharmaceuticals and personal care products (PPCPs) are widely used in daily life throughout the world [1], which lead to their frequent detection in different environments [2; 3; 4]. Hence, PPCPs have been recognized as emerging pollutants, whose potential adverse effects on nontarget organisms have drawn more and more attention [5; 6].  
Carbamazepine (CBZ) has been widely used in the treatment of epilepsy, psychomotor attacks, and trigeminal neuralgia effects [7]. Its annual consumption consists of over 1000 tons [8]. Approximately 30% of oral CBZ dosage is excreted in urine and feces in its unaltered form [8]. In addition, the conventional treatment process in wastewater treatment plants (WWTPs) was found to be invalid for its removal [9; 10]. Its continuous discharge and long half-life in water leads to its frequent detection in aquatic systems [11]. The concentration of CBZ in aquatic systems was reported to range from 0.03 to 11.6 \(\upmu\)g/L throughout the world [12; 13; 14; 15].  
Previous studies showed that CBZ could have adverse effects on the health of aquatic organisms. Oxidative stress has been reported as an important impact of CBZ on aquatic organisms [16; 17; 18]. Besides, CBZ was also found to cause delay in the first reproduction age in _Daphnia magma_[19], behavioral modification in _Dugesia tigrina_[20], and even endocrine-disrupting effects on _Gobiocyrris rarus_[21].  
However, most research concerning CBZ toxicity to aquatic organisms has focused on its individual effects. Regarding zebrafish, a very limited number of articles describes the combined effect of CBZ with other pollutants. In fact, organisms are exposed to complex mixtures of pollutants that may interact and exert effects quite different from single-compound exposure [22]. The interactions of multiple stressors and related biochemical responses of exposed organisms may be completely different from the mode of action (MoA) of each single pollutant [23].  
PPCPs and metals frequently co-occur in aquatic environments [24; 25; 26]. Among these metals, cadmium (Cd) is on the list of priority substances Annex I of the Directive 2013/39/EU. Cd is widely applied in industry, which leads to its rapid release into aquatic systems; this has aroused wide public concerns in recent years [27]. [PERSON] et al. reported that Cd was detected in coastal waters of Kalpakkam on southeast coast of India, with a concentration of 1.6 \(\pm\) 0.15 \(\upmu\)g/L [28]. [PERSON] et al. mentioned in their paper that the concentration of Cd in water samples of the Romanian coastline of the Black Sea was 0.41-50 \(\upmu\)g/L [29]. [PERSON] et al. reported that the concentration of Cd in sea water ranged from 1.5 to 3.65 ng/L [30]. The adverse effects of single exposure to Cd are a well-known issue [31; 32; 33]. However, few studies can be found which investigate the impacts induced by the combination of Cd with PPCPs [34; 35; 36].  
Despite the available toxicity data for Cd and CBZ [37], to our best knowledge, no research has evaluated their combined adverse effects on zebrafish. In the present study, we aimed to evaluate the single and combined effects of these two pollutants on several biomarkers involved in different biochemical process, such as antioxidant systems, energy metabolism, nervous system, and reproduction/endocrine disruption in zebrafish, by exposing female zebrafish to environmentally relevant concentrations for ten days.